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Desando G, Tschon M, Martini L, Sartori M, Giavaresi G, Fini M, Cellamare A, Soranzo C, Longinotti C, D’Alessandro M, Roseti L, Grigolo B. 3D connective micro-fragment enriched with stromal vascular fraction in osteoarthritis: chondroprotective evidence in a preclinical in vivo model. Front Cell Dev Biol 2025; 13:1533405. [PMID: 40083665 PMCID: PMC11903414 DOI: 10.3389/fcell.2025.1533405] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2024] [Accepted: 02/10/2025] [Indexed: 03/16/2025] Open
Abstract
Introduction Adipose-derived cell therapies are one of the most common regenerative therapeutic options to alleviate the multi-component damage of osteoarthritis (OA). Adipose stromal vascular fraction (SVF) has gained scientific consensus for its ability to interact protectively with the joint microenvironment. Recently, the wide range of enzyme-free tissue processing systems has outperformed classical treatments, because of their ability to produce connective micrografts enriched with the SVF (mctSVF). This preclinical in vivo study evaluates the chondroprotective potential of a newly generated mctSVF compared with in vitro expanded adipose stromal cells (ASC) in OA. Methods A mild grade of OA was induced through bilateral anterior cruciate ligament transection (ACLT) surgery in 32 Specific Pathogen Free (SPF) Crl: KBL (NZW) male rabbits followed by the surgical excision of inguinal adipose tissue. After 2 months, OA joints were treated with an intra-articular (IA) injection of mctSVF or ASC. Local biodistribution analysis was used to determine migration patterns of PKH26-labelled cells in the knee joint after 1 month. Efficacy was assessed by gross analysis, histology and immunohistochemistry on the osteochondral unit, synovial membrane and meniscus. Results We elucidate the effectiveness of a one-step approach based on mechanical isolation of mctSVF. Through epifluorescence analysis, we found a similar pattern of cell distribution between cell treatments, mainly towards articular cartilage. Similar regenerative responses were observed in all experimental groups. These effects included: (i) osteochondral repair (promotion of typical anabolic markers and reduction of catabolic ones); (ii) reduction of synovial reactions (reduced synovial hypertrophy and inflammation, and change of macrophage phenotype to a more regenerative one); and (iii) reduction of degenerative changes in the meniscus (reduction of tears). Discussion Our study demonstrates the validity of a novel mechanical system for the generation of the mctSVF micrograft with chondroprotective potential in a preclinical model of moderate OA. The resulting final product can counteract inflammatory processes beyond the OA microenvironment and protect cartilage through the colonization of its structure. The intact and active microanatomy of mctSVF makes it a suitable candidate for translational medicine to treat OA without the need for cell manipulation as with ASC.
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Affiliation(s)
- Giovanna Desando
- IRCCS Istituto Ortopedico Rizzoli, Laboratorio RAMSES, Bologna, Italy
| | - Matilde Tschon
- IRCCS Istituto Ortopedico Rizzoli, Scienze e Tecnologie Chirurgiche, Bologna, Italy
| | - Lucia Martini
- IRCCS Istituto Ortopedico Rizzoli, Scienze e Tecnologie Chirurgiche, Bologna, Italy
| | - Maria Sartori
- IRCCS Istituto Ortopedico Rizzoli, Scienze e Tecnologie Chirurgiche, Bologna, Italy
| | - Gianluca Giavaresi
- IRCCS Istituto Ortopedico Rizzoli, Scienze e Tecnologie Chirurgiche, Bologna, Italy
| | - Milena Fini
- IRCCS Istituto Ortopedico Rizzoli, Scientific Director, Bologna, Italy
| | | | | | | | | | - Livia Roseti
- IRCCS Istituto Ortopedico Rizzoli, Laboratorio RAMSES, Bologna, Italy
| | - Brunella Grigolo
- IRCCS Istituto Ortopedico Rizzoli, Laboratorio RAMSES, Bologna, Italy
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Behn A, Brendle S, Ehrnsperger M, Zborilova M, Grupp TM, Grifka J, Schäfer N, Grässel S. Filtered and unfiltered lipoaspirates reveal novel molecular insights and therapeutic potential for osteoarthritis treatment: a preclinical in vitro study. Front Cell Dev Biol 2025; 13:1534281. [PMID: 40083666 PMCID: PMC11903472 DOI: 10.3389/fcell.2025.1534281] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Accepted: 02/05/2025] [Indexed: 03/16/2025] Open
Abstract
Introduction Orthobiologics, such as autologous nanofat, are emerging as a potential treatment option for osteoarthritis (OA), a common degenerative joint causing pain and disability in the elderly. Nanofat, a minimally processed human fat graft rich in stromal vascular fraction (SVF) secretory factors, has shown promise in relieving pain. This study aimed to elucidate the molecular mechanisms underlying nanofat treatment of OA-affected cells and compare two filtration systems used for nanofat preparation. Methods Chondrocytes and synoviocytes were isolated from articular cartilage and synovium of 22 OA-patients. Lipoaspirates from 13 OA-patients were emulsified using the Adinizer® or Lipocube™ Nano filter systems to generate nanofat. The fluid phase of SVF from both filtered and unfiltered lipoaspirates was applied to OA-affected cells. Luminex multiplex ELISA were performed with lipoaspirates and cell supernatants alongside functional assays evaluating cell migration, proliferation, metabolic activity, and senescence. Results A total of 62 cytokines, chemokines, growth factors, neuropeptides, matrix-degrading enzymes, and complement components were identified in lipoaspirates. Among these, significant concentration differences were observed for TIMP-2, TGF-ß3, and complement component C3 between the filtered and unfiltered samples. Nanofat enhanced chondrocyte proliferation and migration, as well as synoviocyte migration and metabolic activity, while reducing chondrocyte metabolic activity. Pain-related factors like β-NGF, MCP-1, Substance P, VEGF, and αCGRP were reduced, while anti-inflammatory TGF-β1+3 increased and pro-inflammatory cytokines (IL-5, IL-7, IL-15, and IFN-γ) decreased. Nanofat also elevated secretion of complement components and TIMPs in both cell types. Notably, our results revealed no significant differences in cellular effects between sSVF filtered using the Adinizer® and Lipocube™ Nano systems, as well as compared to unfiltered sSVF. Discussion Here, we provide first insights into how autologous nanofat therapy may ameliorate OA by enhancing chondrocyte proliferation and synoviocyte migration while modulating inflammatory and pain-related factors. However, further research is needed to determine its effects on cartilage regeneration.
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Affiliation(s)
- Alissa Behn
- Department of Orthopaedic Surgery, Experimental Orthopaedics, Centre for Medical Biotechnology (ZMB/Biopark 1), University of Regensburg, Regensburg, Germany
| | - Saskia Brendle
- Research and Development, Aesculap AG, Tuttlingen, Germany
- Department of Orthopaedic and Trauma Surgery, Musculoskeletal University Center Munich (MUM), LMU Munich, Munich, Germany
| | - Marianne Ehrnsperger
- Department of Orthopedic Surgery, University of Regensburg, Asklepios, Germany
- Department of Trauma Surgery, University Medical Center Regensburg, Regensburg, Germany
| | - Magdalena Zborilova
- Department of Orthopedic Surgery, University of Regensburg, Asklepios, Germany
| | - Thomas M. Grupp
- Research and Development, Aesculap AG, Tuttlingen, Germany
- Department of Orthopaedic and Trauma Surgery, Musculoskeletal University Center Munich (MUM), LMU Munich, Munich, Germany
| | - Joachim Grifka
- Department of Orthopedic Surgery, University of Regensburg, Asklepios, Germany
- Department of Orthopedics and Ergonomics, Ostbayerische Technische Hochschule (OTH), Regensburg, Germany
| | - Nicole Schäfer
- Department of Orthopaedic Surgery, Experimental Orthopaedics, Centre for Medical Biotechnology (ZMB/Biopark 1), University of Regensburg, Regensburg, Germany
| | - Susanne Grässel
- Department of Orthopaedic Surgery, Experimental Orthopaedics, Centre for Medical Biotechnology (ZMB/Biopark 1), University of Regensburg, Regensburg, Germany
- Department of Orthopedic Surgery, University of Regensburg, Asklepios, Germany
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Gentile P. Reply to "Letter on Lipofilling Enriched with Adipose-Derived Mesenchymal Stem Cells Improves Soft Tissue Deformities and Reduces Scar Pigmentation: Clinical and Instrumental Evaluation in Plastic Surgery". Aesthetic Plast Surg 2025; 49:1001-1002. [PMID: 38168821 DOI: 10.1007/s00266-023-03807-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2023] [Accepted: 12/04/2023] [Indexed: 01/05/2024]
Affiliation(s)
- Pietro Gentile
- Department of Surgical Science, Tor Vergata" University, Via Montpellier 1, 00173, Rome, Italy.
- Academy of International Regenerative Medicine & Surgery Societies (AIRMESS), 1201, Geneva, Switzerland.
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Jeyaraman N, Shrivastava S, Ravi VR, Nallakumarasamy A, Jeyaraman M. Current status of nanofat in the management of knee osteoarthritis: A systematic review. World J Orthop 2025; 16:99690. [PMID: 39850037 PMCID: PMC11752481 DOI: 10.5312/wjo.v16.i1.99690] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2024] [Revised: 12/07/2024] [Accepted: 12/25/2024] [Indexed: 01/13/2025] Open
Abstract
BACKGROUND Osteoarthritis (OA) is a prevalent joint disorder requiring innovative treatment approaches. AIM To evaluate the use of nanofat, a specialized form of adipose tissue-derived cells, in the treatment of OA, by examining its efficacy, safety profile, mechanisms of action, comparative effectiveness, and long-term outcomes. METHODS A comprehensive review of preclinical studies, clinical trials, and in vitro investigations was conducted. The included studies provided insights into the potential role of nanofat in OA treatment, addressing its efficacy, safety profile, mechanisms of action, comparative effectiveness, and long-term outcomes. RESULTS Clinical studies consistently reported the efficacy of nanofat in providing pain relief and functional improvement in patients with OA. Local adverse events were limited to the injection site, such as localized pain and inflammation, and resolved within a few days to weeks. Systemic adverse events were rare, and no significant long-term complications were observed. Mechanistically, nanofat was found to enhance chondrocyte proliferation, reduce inflammation, and promote angiogenesis, thereby contributing to its therapeutic effects. CONCLUSION Nanofat therapy holds promise as a therapeutic option for managing OA, providing pain relief, functional improvement, and potential tissue regeneration. The safety profile of nanofat treatment appears favorable, but long-term data are still limited. Standardized protocols, larger randomized controlled trials, longer follow-up periods, and cost-effectiveness evaluations are warranted to establish optimal protocols, comparative effectiveness, and long-term outcomes. Despite current limitations, nanofat therapy demonstrates translational potential and should be considered in clinical practice for OA treatment, with careful patient selection and monitoring.
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Affiliation(s)
- Naveen Jeyaraman
- Department of Orthopaedics, Datta Meghe Institute of Higher Education and Research, Wardha 442004, Maharashtra, India
- Department of Regenerative Medicine, Mother Cell Regenerative Centre, Tiruchirappalli 620017, Tamil Nadu, India
| | - Sandeep Shrivastava
- Department of Orthopaedics, Datta Meghe Institute of Higher Education and Research, Wardha 442004, Maharashtra, India
| | - VR Ravi
- Department of Regenerative Medicine, Mother Cell Regenerative Centre, Tiruchirappalli 620017, Tamil Nadu, India
| | - Arulkumar Nallakumarasamy
- Department of Orthopaedics, Datta Meghe Institute of Higher Education and Research, Wardha 442004, Maharashtra, India
- Department of Regenerative Medicine, Mother Cell Regenerative Centre, Tiruchirappalli 620017, Tamil Nadu, India
| | - Madhan Jeyaraman
- Department of Regenerative Medicine, Mother Cell Regenerative Centre, Tiruchirappalli 620017, Tamil Nadu, India
- Department of Orthopaedics, ACS Medical College and Hospital, Dr MGR Educational and Research Institute, Chennai 600077, Tamil Nadu, India
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Karina K, Biben JA, Ekaputri K, Krisandi G, Rosadi I, Sobariah S, Afini I, Widyastuti T, Zakiyah A, Ernanda D. Revisiting Fat Graft Harvesting and Processing Technique to Optimize Its Regenerative Potential. PLASTIC AND RECONSTRUCTIVE SURGERY-GLOBAL OPEN 2025; 13:e6420. [PMID: 39802276 PMCID: PMC11723667 DOI: 10.1097/gox.0000000000006420] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2024] [Accepted: 10/31/2024] [Indexed: 01/16/2025]
Abstract
Background The use of fat grafting has expanded to include cell and tissue regeneration, necessitating investigations to ensure the viability of stromal and adipose-derived mesenchymal stem cells (ASCs) within the transferred fat parcels. This study explored the impact of harvesting technique and centrifugation on the viability of stromal cells and ASCs in lipoaspirate. Methods Fat was harvested from patients undergoing fat grafting using 2 types of liposuction cannula: (A) a 3-mm blunt tip cannula with 3 smooth holes and (B) a 2.4-mm, sharp point port, multihole blunt tip cannula. Fat from cannula B underwent different processing methods: no centrifugation, 300g, 600g, and 900g centrifugation. Stromal cells were isolated, quantified, and evaluated for viability. ASCs were cultured from these samples to confirm survival. Results Lipoaspirates from 21 patients were analyzed. The mean stromal cell counts were 0.937 × 109 ± 0.346 × 109/mL for cannula A and 0.734 × 109 ± 0.266 × 109/mL for cannula B (P = 0.684), with viabilities of 98.79% and 98.22% (P = 0.631), respectively. ASCs isolated and after 2-passage culture were also higher for cannula A. Stromal cell quantification and viability were lowest in the noncentrifuged group (P < 0.05) and highest in the 600g centrifugation group. Conclusions Fat harvesting using cannulas A and B showed no significant difference in stromal cell yield or viability. Handheld syringe liposuction preserved stromal vascular fraction cell and ASC viability. Centrifugation at different speeds did not significantly affect stromal cell viability.
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Affiliation(s)
- Karina Karina
- From the Division of Plastic Surgery, Hayandra Clinic, Hayandra Peduli Foundation, Jakarta, Indonesia
- HayandraLab, Hayandra Peduli Foundation, Jakarta, Indonesia
- Faculty of Medicine, Universitas Pembangunan Nasional Veteran Jakarta, Jakarta, Indonesia
- Research Center for Regenerative Medicine & Neuroscience, Faculty of Medicine, Universitas Pembangunan Nasional Veteran Jakarta, Jakarta, Indonesia
| | - Johannes A. Biben
- From the Division of Plastic Surgery, Hayandra Clinic, Hayandra Peduli Foundation, Jakarta, Indonesia
| | - Krista Ekaputri
- From the Division of Plastic Surgery, Hayandra Clinic, Hayandra Peduli Foundation, Jakarta, Indonesia
| | - Grady Krisandi
- HayandraLab, Hayandra Peduli Foundation, Jakarta, Indonesia
- Faculty of Medicine, University of Indonesia, Jakarta, Indonesia
| | - Imam Rosadi
- HayandraLab, Hayandra Peduli Foundation, Jakarta, Indonesia
- Department of Biology, Faculty of Mathematics and Natural Sciences, Mulawarman University, Samarinda, Indonesia
| | - Siti Sobariah
- HayandraLab, Hayandra Peduli Foundation, Jakarta, Indonesia
| | - Irsyah Afini
- HayandraLab, Hayandra Peduli Foundation, Jakarta, Indonesia
- Faculty of Medicine, University of Indonesia, Jakarta, Indonesia
| | | | - Alfida Zakiyah
- HayandraLab, Hayandra Peduli Foundation, Jakarta, Indonesia
| | - Difky Ernanda
- HayandraLab, Hayandra Peduli Foundation, Jakarta, Indonesia
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Bonomi F, Limido E, Weinzierl A, Ampofo E, Harder Y, Menger MD, Laschke MW. Nanofat Improves Vascularization and Tissue Integration of Dermal Substitutes without Affecting Their Biocompatibility. J Funct Biomater 2024; 15:294. [PMID: 39452592 PMCID: PMC11508499 DOI: 10.3390/jfb15100294] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2024] [Revised: 09/29/2024] [Accepted: 10/01/2024] [Indexed: 10/26/2024] Open
Abstract
Dermal substitutes require sufficient tissue integration and vascularization to be successfully covered with split-thickness skin grafts. To rapidly achieve this, we provide the proof of principle for a novel vascularization strategy with high translational potential. Nanofat was generated from subcutaneous adipose tissue of green fluorescence protein (GFP)+ C57BL/6J donor mice and seeded onto small samples (4 mm in diameter) of the clinically approved dermal substitute Integra®. These samples and non-seeded controls were then implanted into full-thickness skin defects in the dorsal skinfold chamber of C57BL/6J wild-type mice and analyzed by intravital fluorescence microscopy, histology and immunohistochemistry over a 14-day period. Nanofat-seeded dermal substitutes exhibited an accelerated vascularization, as indicated by a significantly higher functional microvessel density on days 10 and 14 when compared to controls. This was primarily caused by the reassembly of GFP+ microvascular fragments inside the nanofat into microvascular networks. The improved vascularization promoted integration of the implants into the surrounding host tissue, which finally exhibited an increased formation of a collagen-rich granulation tissue. There were no marked differences in the inflammatory host tissue reaction to nanofat-seeded and control implants. These findings demonstrate that nanofat significantly improves the in vivo performance of dermal substitutes without affecting their biocompatibility.
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Affiliation(s)
- Francesca Bonomi
- Institute for Clinical and Experimental Surgery, Saarland University, 66421 Homburg, Germany; (F.B.); (E.L.); (A.W.); (E.A.); (M.D.M.)
| | - Ettore Limido
- Institute for Clinical and Experimental Surgery, Saarland University, 66421 Homburg, Germany; (F.B.); (E.L.); (A.W.); (E.A.); (M.D.M.)
- Department of Surgery, Ospedale Beata Vergine Mendrisio, Ente Ospedaliero Cantonale (EOC), 6850 Mendrisio, Switzerland
| | - Andrea Weinzierl
- Institute for Clinical and Experimental Surgery, Saarland University, 66421 Homburg, Germany; (F.B.); (E.L.); (A.W.); (E.A.); (M.D.M.)
- Department of Plastic Surgery and Hand Surgery, University Hospital Zurich, 8006 Zurich, Switzerland
| | - Emmanuel Ampofo
- Institute for Clinical and Experimental Surgery, Saarland University, 66421 Homburg, Germany; (F.B.); (E.L.); (A.W.); (E.A.); (M.D.M.)
| | - Yves Harder
- Department of Plastic, Reconstructive and Aesthetic Surgery and Hand Surgery, Centre Hospitalier Universitaire Vaudois (CHUV), 1005 Lausanne, Switzerland;
- Faculty of Biology and Medicine, University of Lausanne (UNIL), 1005 Lausanne, Switzerland
| | - Michael D. Menger
- Institute for Clinical and Experimental Surgery, Saarland University, 66421 Homburg, Germany; (F.B.); (E.L.); (A.W.); (E.A.); (M.D.M.)
| | - Matthias W. Laschke
- Institute for Clinical and Experimental Surgery, Saarland University, 66421 Homburg, Germany; (F.B.); (E.L.); (A.W.); (E.A.); (M.D.M.)
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Di Rocco G, Trivisonno A, Trivisonno G, Toietta G. Dissecting human adipose tissue heterogeneity using single-cell omics technologies. Stem Cell Res Ther 2024; 15:322. [PMID: 39334440 PMCID: PMC11437900 DOI: 10.1186/s13287-024-03931-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2024] [Accepted: 09/09/2024] [Indexed: 09/30/2024] Open
Abstract
Single-cell omics technologies that profile genes (genomic and epigenomic) and determine the abundance of mRNA (transcriptomic), protein (proteomic and secretomic), lipids (lipidomic), and extracellular matrix (matrisomic) support the dissection of adipose tissue heterogeneity at unprecedented resolution in a temporally and spatially defined manner. In particular, cell omics technologies may provide innovative biomarkers for the identification of rare specific progenitor cell subpopulations, assess transcriptional and proteomic changes affecting cell proliferation and immunomodulatory potential, and accurately define the lineage hierarchy and differentiation status of progenitor cells. Unraveling adipose tissue complexity may also provide for the precise assessment of a dysfunctional state, which has been associated with cancer, as cancer-associated adipocytes play an important role in shaping the tumor microenvironment supporting tumor progression and metastasis, obesity, metabolic syndrome, and type 2 diabetes mellitus. The information collected by single-cell omics has relevant implications for regenerative medicine because adipose tissue is an accessible source of multipotent cells; alternative cell-free approaches, including the use of adipose tissue stromal cell-conditioned medium, extracellular vesicles, or decellularized extracellular matrix, are clinically valid options. Subcutaneous white adipose tissue, which is generally harvested via liposuction, is highly heterogeneous because of intrinsic biological variability and extrinsic inconsistencies in the harvesting and processing procedures. The current limited understanding of adipose tissue heterogeneity impinges on the definition of quality standards appropriate for clinical translation, which requires consistency and uniformity of the administered product. We review the methods used for dissecting adipose tissue heterogeneity and provide an overview of advances in omics technology that may contribute to the exploration of heterogeneity and dynamics of adipose tissue at the single-cell level.
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Affiliation(s)
- Giuliana Di Rocco
- Unit of Cellular Networks and Molecular Therapeutic Targets, IRCCS Regina Elena National Cancer Institute, 00144, Rome, Italy
| | - Angelo Trivisonno
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168, Rome, Italy
| | | | - Gabriele Toietta
- Tumor Immunology and Immunotherapy Unit, IRCCS Regina Elena National Cancer Institute, Via E. Chianesi, 53, 00144, Rome, Italy.
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Potenza AE, Nachira D, Sacchetti F, Trivisonno A, Pugliese D, Boškoski I, Caudullo G, Minordi LM, Larosa L, Caprino P, Scaldaferri F, Sofo L, Porziella V. Effectiveness of autologous emulsified stromal vascular fraction tissue injection for the treatment of complex perianal fistulas in inflammatory bowel diseases patients: a pilot study. Therap Adv Gastroenterol 2024; 17:17562848241263014. [PMID: 39239070 PMCID: PMC11375657 DOI: 10.1177/17562848241263014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2023] [Accepted: 06/03/2024] [Indexed: 09/07/2024] Open
Abstract
Complex fistulizing perianal disease is a disabling manifestation of inflammatory bowel disease (IBD), seriously compromising patients 'quality of life'. The success rate of available treatments is quite low, and nearly half of the patients will develop chronically active fistulas or experience fistula recurrence. Mesenchymal stem cell therapy has shown interesting results, but the complexity and the cost of production limit its widespread use. This study aims to report the results of the innovative use of autologous emulsified adipose-derived stromal vascular fraction tissue for treating complex fistulizing perianal disease. From March 2021 to March 2022, 10 patients underwent a two-step procedure: (1) examination under anaesthesia, with loose seton drainage and 4 weeks later and (2) curettage of the fistulous tract, internal fistula closure and an injection of autologous emulsified adipose-derived stromal vascular fraction tissue harvested from the subcutaneous layer of the patient's hip. Clinical and radiological (through magnetic resonance imaging) healing were assessed at 6 months. We included five patients affected by Crohn's disease, three by ulcerative colitis and two by indeterminate colitis. All patients were on concomitant biological therapy (50% on Infliximab). One patient required a re-treatment for a relapse and two different fistulas were separately treated in another one. Out of 12 total procedures performed, clinical healing was achieved in 10 cases (83%), while radiological healing in 6 patients (50%). No adverse events were recorded. Autologous emulsified adipose-derived stromal vascular fraction tissue can represent an effective, safe and cheap add-on therapy for patients with complex perianal fistulas in IBDs.
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Affiliation(s)
- Angelo Eugenio Potenza
- Abdominal Surgery Unit, Department of Gastroenterological, Endocrine-Metabolic and Nephro-Urological Sciences, Fondazione Policlinico Universitario 'A. Gemelli' IRCCS, Rome, Italy
| | - Dania Nachira
- Department of General Thoracic Surgery, Fondazione Policlinico Universitario 'A. Gemelli' IRCCS, Università Cattolica del Sacro Cuore, Roma, Italy
| | - Franco Sacchetti
- Abdominal Surgery Unit, Department of Gastroenterological, Endocrine-Metabolic and Nephro-Urological Sciences, Fondazione Policlinico Universitario 'A. Gemelli' IRCCS, L. go A. Gemelli 8, Rome 00168, Italy
| | - Angelo Trivisonno
- Unit of Plastic Surgery, Assunzione di Maria Santissima Clinic, Rome, Italy
| | - Daniela Pugliese
- IBD Unit, CEMAD Centro Malattie dell'Apparato Digerente, Medicina Interna e Gastroenterologia Fondazione Policlinico Universitario Gemelli IRCCS, Roma, Italy
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Roma, Italy
| | - Ivo Boškoski
- Center for Endoscopic Research Therapeutics and Training, Università Cattolica del Sacro Cuore, Rome, Italy
- Digestive Endoscopy Unit, Fondazione Policlinico Universitario 'A. Gemelli' IRCCS, Rome, Italy
| | - Giuseppe Caudullo
- School of General Surgery, Università Cattolica del Sacro Cuore, Roma, Italy
| | - Laura Maria Minordi
- Department of Diagnostic Imaging, Oncological Radiotherapy, and Hematology, Fondazione Policlinico Universitario 'A. Gemelli' IRCCS, Rome, Italy
| | - Luigi Larosa
- Department of Diagnostic Imaging, Oncological Radiotherapy, and Hematology, Fondazione Policlinico Universitario 'A. Gemelli' IRCCS, Rome, Italy
| | - Paola Caprino
- Abdominal Surgery Unit, Department of Gastroenterological, Endocrine-Metabolic and Nephro-Urological Sciences, Fondazione Policlinico Universitario 'A. Gemelli' IRCCS, Rome, Italy
| | - Franco Scaldaferri
- IBD Unit, CEMAD Centro Malattie dell'Apparato Digerente, Medicina Interna e Gastroenterologia Fondazione Policlinico Universitario Gemelli IRCCS, Roma, Italy
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Roma, Italy
| | - Luigi Sofo
- Abdominal Surgery Unit, Department of Gastroenterological, Endocrine-Metabolic and Nephro-Urological Sciences, Fondazione Policlinico Universitario 'A. Gemelli' IRCCS, Università Cattolica del Sacro Cuore, Roma, Italy
| | - Venanzio Porziella
- Department of General Thoracic Surgery, Fondazione Policlinico Universitario 'A. Gemelli' IRCCS, Università Cattolica del Sacro Cuore, Roma, Italy
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Xiao Y, Nie M, Xu W, Zhang J, Lei S, Wu D. The efficiency of human fat products in wound healing: A systematic review and meta-analysis. Int Wound J 2024; 21:e70016. [PMID: 39216014 PMCID: PMC11365526 DOI: 10.1111/iwj.70016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2024] [Revised: 07/14/2024] [Accepted: 07/25/2024] [Indexed: 09/04/2024] Open
Abstract
Wound development and healing involve intricate genetic and molecular processes, posing significant clinical management challenges. The objective of this study was to assess commonly used fat extracts' efficacy and safety (autologous fat, stromal vascular fraction and adipose-derived stem cells) in wound healing, particularly for refractory wounds, with the goal of providing evidence in clinical use. After a systematic review, 21 randomised controlled trials were included in our study. Based on the classification of human fat products, our meta-analysis revealed that the use of human fat products could speed healing rate, shorten healing time and achieve more complete healing, with statistically significant differences in outcome indicators when compared to conventional treatments. The analysis of histological findings across various studies indicated that fat extracts can promote epithelialization, collagen deposition and vascularization, thereby facilitating tissue regeneration and reducing inflammatory reactions. There were potential benefits to reducing patient pain levels after using adipose extracts. Furthermore, we analysed and summarised adverse events indicating the safe and effective clinical use of human fat products in wound treatment. Our research findings supported the efficiency of human fat products and demonstrated a high degree of safety in the clinical practice of wound management.
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Affiliation(s)
- Yutian Xiao
- Department of Plastic and Cosmetic Surgery, Xiangya HospitalCentral South UniversityChangshaPR China
- National Clinical Research Center for Geriatric DisordersXiangya HospitalChangshaPR China
| | - Mengqi Nie
- Department of Plastic and Cosmetic Surgery, Xiangya HospitalCentral South UniversityChangshaPR China
- National Clinical Research Center for Geriatric DisordersXiangya HospitalChangshaPR China
| | - Wenqing Xu
- Department of Plastic and Cosmetic Surgery, Xiangya HospitalCentral South UniversityChangshaPR China
- National Clinical Research Center for Geriatric DisordersXiangya HospitalChangshaPR China
| | - Jinglve Zhang
- Department of Plastic and Cosmetic Surgery, Xiangya HospitalCentral South UniversityChangshaPR China
- National Clinical Research Center for Geriatric DisordersXiangya HospitalChangshaPR China
| | - Shaorong Lei
- Department of Plastic and Cosmetic Surgery, Xiangya HospitalCentral South UniversityChangshaPR China
- National Clinical Research Center for Geriatric DisordersXiangya HospitalChangshaPR China
| | - Dingyu Wu
- Department of Plastic and Cosmetic Surgery, Xiangya HospitalCentral South UniversityChangshaPR China
- National Clinical Research Center for Geriatric DisordersXiangya HospitalChangshaPR China
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10
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Tran VVT, Jin X, Hong KY, Chang H. Effects of Nanofat in Plastic and Reconstructive Surgery: A Systematic Review. Plast Reconstr Surg 2024; 154:451e-464e. [PMID: 37400953 DOI: 10.1097/prs.0000000000010905] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/05/2023]
Abstract
BACKGROUND Since nanofat was first introduced by Tonnard in 2013, numerous studies have reported positive findings with its use; however, concerns exist regarding its effects and mechanisms, and the various methods used to generate nanofat also remain unclear. The authors conducted a systematic review to evaluate the efficacy of nanofat grafting alone in plastic and reconstructive surgery. METHODS The MEDLINE, Embase, Cochrane Central, Web of Science, and Scopus databases were searched for studies related to the use of nanofat grafting alone in plastic and reconstructive surgery. Outcomes of interest were all clinical results in humans or animals. RESULTS Twelve studies were included. No meta-analysis was conducted due to the clinical heterogeneity of the studies. In general, included studies had a low level of evidence. Six studies ( n = 253 patients) showed significant improvements in scar characteristics based on Patient and Observer Scar Assessment Scale, FACE-Q scale, physician assessment, patient satisfaction, and Vancouver Scar Scale scores. Four studies described the benefits of nanofat in skin rejuvenation (wrinkles, fine rhytides, pigmentation, and discoloration) through photographs, questionnaires, and indentation indices. Histologic evaluation illustrated overall increases in skin thickness, collagen, and elastic fibers. Three experimental studies showed the beneficial effects of nanofat on fat grafting, diabetic wound healing, and hair growth, with compelling histological evidence. No severe complication was reported. CONCLUSIONS Nanofat grafting shows potential benefits in scar and antiaging treatments, with conclusive histological evidence. Clinical studies of fat grafting, wound healing, and hair growth should be conducted, based on the results of this systematic review. Nanofat grafting could be a practical and safe procedure.
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Affiliation(s)
- Vinh Vuong The Tran
- From the Hi-Tech Center, Vinmec Healthcare System
- Department of Plastic and Reconstructive Surgery, Seoul National University College of Medicine
| | - Xian Jin
- Department of Plastic and Reconstructive Surgery, Seoul National University College of Medicine
| | - Ki Yong Hong
- Department of Plastic and Reconstructive Surgery, Seoul National University Hospital, Seoul National University College of Medicine
| | - Hak Chang
- Department of Plastic and Reconstructive Surgery, Seoul National University Hospital, Seoul National University College of Medicine
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11
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Lau CS, Park SY, Ethiraj LP, Singh P, Raj G, Quek J, Prasadh S, Choo Y, Goh BT. Role of Adipose-Derived Mesenchymal Stem Cells in Bone Regeneration. Int J Mol Sci 2024; 25:6805. [PMID: 38928517 PMCID: PMC11204188 DOI: 10.3390/ijms25126805] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Revised: 06/13/2024] [Accepted: 06/14/2024] [Indexed: 06/28/2024] Open
Abstract
Bone regeneration involves multiple factors such as tissue interactions, an inflammatory response, and vessel formation. In the event of diseases, old age, lifestyle, or trauma, bone regeneration can be impaired which could result in a prolonged healing duration or requiring an external intervention for repair. Currently, bone grafts hold the golden standard for bone regeneration. However, several limitations hinder its clinical applications, e.g., donor site morbidity, an insufficient tissue volume, and uncertain post-operative outcomes. Bone tissue engineering, involving stem cells seeded onto scaffolds, has thus been a promising treatment alternative for bone regeneration. Adipose-derived mesenchymal stem cells (AD-MSCs) are known to hold therapeutic value for the treatment of various clinical conditions and have displayed feasibility and significant effectiveness due to their ease of isolation, non-invasive, abundance in quantity, and osteogenic capacity. Notably, in vitro studies showed AD-MSCs holding a high proliferation capacity, multi-differentiation potential through the release of a variety of factors, and extracellular vesicles, allowing them to repair damaged tissues. In vivo and clinical studies showed AD-MSCs favoring better vascularization and the integration of the scaffolds, while the presence of scaffolds has enhanced the osteogenesis potential of AD-MSCs, thus yielding optimal bone formation outcomes. Effective bone regeneration requires the interplay of both AD-MSCs and scaffolds (material, pore size) to improve the osteogenic and vasculogenic capacity. This review presents the advances and applications of AD-MSCs for bone regeneration and bone tissue engineering, focusing on the in vitro, in vivo, and clinical studies involving AD-MSCs for bone tissue engineering.
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Affiliation(s)
- Chau Sang Lau
- National Dental Centre Singapore, National Dental Research Institute Singapore, Singapore 168938, Singapore; (C.S.L.); (S.Y.P.); (L.P.E.); (G.R.)
- Oral Health Academic Clinical Programme, Duke-NUS Medical School, Singapore 169857, Singapore
| | - So Yeon Park
- National Dental Centre Singapore, National Dental Research Institute Singapore, Singapore 168938, Singapore; (C.S.L.); (S.Y.P.); (L.P.E.); (G.R.)
| | - Lalith Prabha Ethiraj
- National Dental Centre Singapore, National Dental Research Institute Singapore, Singapore 168938, Singapore; (C.S.L.); (S.Y.P.); (L.P.E.); (G.R.)
- Oral Health Academic Clinical Programme, Duke-NUS Medical School, Singapore 169857, Singapore
| | - Priti Singh
- National Dental Centre Singapore, National Dental Research Institute Singapore, Singapore 168938, Singapore; (C.S.L.); (S.Y.P.); (L.P.E.); (G.R.)
| | - Grace Raj
- National Dental Centre Singapore, National Dental Research Institute Singapore, Singapore 168938, Singapore; (C.S.L.); (S.Y.P.); (L.P.E.); (G.R.)
| | - Jolene Quek
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore; (J.Q.); (Y.C.)
| | - Somasundaram Prasadh
- Center for Clean Energy Engineering, University of Connecticut, Storrs, CT 06269, USA;
| | - Yen Choo
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore; (J.Q.); (Y.C.)
| | - Bee Tin Goh
- National Dental Centre Singapore, National Dental Research Institute Singapore, Singapore 168938, Singapore; (C.S.L.); (S.Y.P.); (L.P.E.); (G.R.)
- Oral Health Academic Clinical Programme, Duke-NUS Medical School, Singapore 169857, Singapore
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12
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Mundluru VK, Naidu MJ, Mundluru RT, Jeyaraman N, Muthu S, Ramasubramanian S, Jeyaraman M. Non-enzymatic methods for isolation of stromal vascular fraction and adipose-derived stem cells: A systematic review. World J Methodol 2024; 14:94562. [PMID: 38983657 PMCID: PMC11229868 DOI: 10.5662/wjm.v14.i2.94562] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2024] [Revised: 05/03/2024] [Accepted: 05/30/2024] [Indexed: 06/13/2024] Open
Abstract
BACKGROUND Adipose-derived stem cells (ADSCs) and the stromal vascular fraction (SVF) have garnered substantial interest in regenerative medicine due to their potential to treat a wide range of conditions. Traditional enzymatic methods for isolating these cells face challenges such as high costs, lengthy processing time, and regu-latory complexities. AIM This systematic review aimed to assess the efficacy and practicality of non-enzymatic, mechanical methods for isolating SVF and ADSCs, comparing these to conventional enzymatic approaches. METHODS Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a comprehensive literature search was conducted across multiple databases. Studies were selected based on inclusion criteria focused on non-enzymatic isolation methods for SVF and ADSCs from adipose tissue. The risk of bias was assessed, and a qualitative synthesis of findings was performed due to the methodological heterogeneity of the included studies. RESULTS Nineteen studies met the inclusion criteria, highlighting various mechanical techniques such as centrifugation, vortexing, and ultrasonic cavitation. The review identified significant variability in cell yield and viability, and the integrity of isolated cells across different non-enzymatic methods compared to enzymatic procedures. Despite some advantages of mechanical methods, including reduced processing time and avoidance of enzymatic reagents, the evidence suggests a need for optimization to match the cell quality and therapeutic efficacy achievable with enzymatic isolation. CONCLUSION Non-enzymatic, mechanical methods offer a promising alternative to enzymatic isolation of SVF and ADSCs, potentially simplifying the isolation process and reducing regulatory hurdles. However, further research is necessary to standardize these techniques and ensure consistent, high-quality cell yields for clinical applications. The development of efficient, safe, and reproducible non-enzymatic isolation methods could significantly advance the field of regenerative medicine.
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Affiliation(s)
- Vamsi Krishna Mundluru
- Department of Orthopaedics, MJ Naidu Super Speciality Hospital, Vijayawada 520002, Andhra Pradesh, India
- Department of Regenerative Medicine, StemC Clinics, Vijayawada 520002, Andhra Pradesh, India
| | - MJ Naidu
- Department of Orthopaedics, MJ Naidu Super Speciality Hospital, Vijayawada 520002, Andhra Pradesh, India
- Department of Regenerative Medicine, StemC Clinics, Vijayawada 520002, Andhra Pradesh, India
| | - Ravi Teja Mundluru
- Department of Orthopaedics, MJ Naidu Super Speciality Hospital, Vijayawada 520002, Andhra Pradesh, India
- Department of Regenerative Medicine, StemC Clinics, Vijayawada 520002, Andhra Pradesh, India
| | - Naveen Jeyaraman
- Department of Regenerative Medicine, StemC Clinics, Vijayawada 520002, Andhra Pradesh, India
- Department of Orthopaedics, ACS Medical College and Hospital, Dr. MGR Educational and Research Institute, Chennai 600077, Tamil Nadu, India
- Department of Orthopaedics, Orthopaedic Research Group, Coimbatore 641045, Tamil Nadu, India
| | - Sathish Muthu
- Department of Orthopaedics, Orthopaedic Research Group, Coimbatore 641045, Tamil Nadu, India
- Department of Orthopaedics, Government Medical College and Hospital, Karur 639004, Tamil Nadu, India
- Department of Biotechnology, Faculty of Engineering, Karpagam Academy of Higher Education, Coimbatore 641021, Tamil Nadu, India
| | - Swaminathan Ramasubramanian
- Department of Orthopaedics, Government Medical College, Omandurar Government Estate, Chennai 600002, Tamil Nadu, India
| | - Madhan Jeyaraman
- Department of Regenerative Medicine, StemC Clinics, Vijayawada 520002, Andhra Pradesh, India
- Department of Orthopaedics, ACS Medical College and Hospital, Dr. MGR Educational and Research Institute, Chennai 600077, Tamil Nadu, India
- Department of Orthopaedics, Orthopaedic Research Group, Coimbatore 641045, Tamil Nadu, India
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13
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Zannoni F, Caravelli S, Russo A, Perisano C, Greco T, Baiardi A, Di Ponte M, Vocale E, Mosca M. Clinical results in patients affected by moderate-severe knee osteoarthritis and treated with micro-fragmented adipose tissue: the therapeutic effects on symptomatology. Musculoskelet Surg 2024; 108:215-224. [PMID: 38602604 DOI: 10.1007/s12306-024-00816-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2023] [Accepted: 03/23/2024] [Indexed: 04/12/2024]
Abstract
Osteoarthrosis is a degenerative musculoskeletal disease that presents a major public health problem, due to the increasing average age of the active population, as well as the increasing percentage of obesity or overweight of the general population. New therapeutic approaches have been developed, such as regenerative medicine that uses mesenchymal stromal cells taken from adipose tissue. This study analyzed the clinical potential benefits of using autologous adipose tissue to treat patients with moderate-severe knee osteoarthritis.In 2021, a total of 50 knees, affected by moderate-severe knee osteoarthritis, were treated with an intra-articular injection of micro-fragmented subcutaneous adipose tissue. Patients were submitted to the KOOS questionnaire before the operation and one year after the operation and VAS pain score at time 0, 3, 6, 12 months.Of the 50 patients treated, 2 patients were excluded from the study. Of the remaining 48 patients, improvements have been achieved in all subclasses of KOOS. In particular, VAS score proves that improvements are more considerable starting from the 3rd month after surgery.The results obtained in this study show the safety and potential benefit of the use of autologous micro-fragmented adipose on people who are affected by moderate-severe knee osteoarthritis.
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Affiliation(s)
- F Zannoni
- U.O. Ortopedia Bentivoglio, IRCCS Istituto Ortopedico Rizzoli, Bentivoglio (BO), Italy
| | - S Caravelli
- U.O. Ortopedia Bentivoglio, IRCCS Istituto Ortopedico Rizzoli, Bentivoglio (BO), Italy.
| | - A Russo
- II Clinic of Orthopaedics and Traumatology, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
| | - C Perisano
- Department of Ageing, Neurosciences, Head-Neck and Orthopedics Sciences, Orthopedics and Trauma Surgery Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168, Rome, Italy
| | - T Greco
- Department of Ageing, Neurosciences, Head-Neck and Orthopedics Sciences, Orthopedics and Trauma Surgery Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168, Rome, Italy
| | - A Baiardi
- U.O. Ortopedia Bentivoglio, IRCCS Istituto Ortopedico Rizzoli, Bentivoglio (BO), Italy
| | - M Di Ponte
- U.O. Ortopedia Bentivoglio, IRCCS Istituto Ortopedico Rizzoli, Bentivoglio (BO), Italy
| | - E Vocale
- U.O. Ortopedia Bentivoglio, IRCCS Istituto Ortopedico Rizzoli, Bentivoglio (BO), Italy
| | - M Mosca
- U.O. Ortopedia Bentivoglio, IRCCS Istituto Ortopedico Rizzoli, Bentivoglio (BO), Italy
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14
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Holzbauer M, Priglinger E, Kølle SFT, Prantl L, Stadler C, Winkler PW, Gotterbarm T, Duscher D. Intra-Articular Application of Autologous, Fat-Derived Orthobiologics in the Treatment of Knee Osteoarthritis: A Systematic Review. Cells 2024; 13:750. [PMID: 38727286 PMCID: PMC11083621 DOI: 10.3390/cells13090750] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2024] [Revised: 04/21/2024] [Accepted: 04/22/2024] [Indexed: 05/13/2024] Open
Abstract
The aim of this study was to review the current literature regarding the effects of intra-articularly applied, fat-derived orthobiologics (FDO) in the treatment of primary knee osteoarthritis over a mid-term follow-up period. A systematic literature search was conducted on the online databases of Scopus, PubMed, Ovid MEDLINE, and Cochrane Library. Studies investigating intra-articularly applied FDO with a minimum number of 10 knee osteoarthritis patients, a follow-up period of at least 2 years, and at least 1 reported functional parameter (pain level or Patient-Reported Outcome Measures) were included. Exclusion criteria encompassed focal chondral defects and techniques including additional arthroscopic bone marrow stimulation. In 28 of 29 studies, FDO showed a subjective improvement in symptoms (pain and Patient-Reported Outcome Measures) up to a maximum follow-up of 7.2 years. Radiographic cartilage regeneration up to 3 years postoperatively, as well as macroscopic cartilage regeneration investigated via second-look arthroscopy, may corroborate the favorable clinical findings in patients with knee osteoarthritis. The methodological heterogeneity in FDO treatments leads to variations in cell composition and represents a limitation in the current state of knowledge. However, this systematic review suggests that FDO injection leads to beneficial mid-term results including symptom reduction and preservation of the affected joint in knee osteoarthritis patients.
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Affiliation(s)
- Matthias Holzbauer
- Department for Orthopedics and Trauma Surgery, Med Campus III, Kepler University Hospital, Krankenhausstrasse 9, 4020 Linz, Austria; (E.P.); (C.S.); (P.W.W.); (T.G.)
- Faculty of Medicine, Johannes Kepler University Linz, Altenbergerstraße 69, 4040 Linz, Austria
| | - Eleni Priglinger
- Department for Orthopedics and Trauma Surgery, Med Campus III, Kepler University Hospital, Krankenhausstrasse 9, 4020 Linz, Austria; (E.P.); (C.S.); (P.W.W.); (T.G.)
- Faculty of Medicine, Johannes Kepler University Linz, Altenbergerstraße 69, 4040 Linz, Austria
| | | | - Lukas Prantl
- Department of Plastic, Hand and Reconstructive Surgery, University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany; (L.P.); (D.D.)
| | - Christian Stadler
- Department for Orthopedics and Trauma Surgery, Med Campus III, Kepler University Hospital, Krankenhausstrasse 9, 4020 Linz, Austria; (E.P.); (C.S.); (P.W.W.); (T.G.)
- Faculty of Medicine, Johannes Kepler University Linz, Altenbergerstraße 69, 4040 Linz, Austria
| | - Philipp Wilhelm Winkler
- Department for Orthopedics and Trauma Surgery, Med Campus III, Kepler University Hospital, Krankenhausstrasse 9, 4020 Linz, Austria; (E.P.); (C.S.); (P.W.W.); (T.G.)
- Faculty of Medicine, Johannes Kepler University Linz, Altenbergerstraße 69, 4040 Linz, Austria
| | - Tobias Gotterbarm
- Department for Orthopedics and Trauma Surgery, Med Campus III, Kepler University Hospital, Krankenhausstrasse 9, 4020 Linz, Austria; (E.P.); (C.S.); (P.W.W.); (T.G.)
- Faculty of Medicine, Johannes Kepler University Linz, Altenbergerstraße 69, 4040 Linz, Austria
| | - Dominik Duscher
- Department of Plastic, Hand and Reconstructive Surgery, University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany; (L.P.); (D.D.)
- TF Plastic Surgery and Longevity Center, Herzogstrasse 67, 80803 Munich, Germany and Dorotheergasse 12, 1010 Vienna, Austria
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15
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Tran VVT, Hong KY, Jin X, Chang H. Histological Comparison of Nanofat and Lipoconcentrate: Enhanced Effects of Lipoconcentrate on Adipogenesis and Angiogenesis. Aesthetic Plast Surg 2024; 48:752-763. [PMID: 37648930 DOI: 10.1007/s00266-023-03583-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2023] [Accepted: 07/26/2023] [Indexed: 09/01/2023]
Abstract
BACKGROUND Nanofat and lipoconcentrate contain adipose-derived stem cells and growth factors, and have wide clinical applications in the regenerative field. This study aimed to investigate the microenvironmental changes associated with nanofat and lipoconcentrate. METHODS Conventional fat, nanofat, or lipoconcentrate (0.2 mL each, n = 5 per group) were injected subcutaneously into the dorsal flanks of athymic nude mice. The graft weights were measured at postoperative week 4; the grafts and their overlying skin were used for histological analyses. RESULTS Weights of the lipoconcentrate grafts were significantly greater than those of the conventional fat (p < 0.05) and nanofat (p < 0.01) grafts. There was no significant difference in inflammation, oil cysts, and fibrosis between the conventional fat and nanofat groups. Histological examination of the lipoconcentrate grafts showed less macrophage infiltration and the formation of fibrosis and oil cysts. Additionally, adipogenesis and angiogenesis were induced more in the lipoconcentrate grafts than in the nanofat grafts (p < 0.01). Lipoconcentrate and nanofat improved dermal thickness (p < 0.001 and p < 0.01, respectively, versus the baseline). CONCLUSION Lipoconcentrate grafts had greater volume and shape retention than conventional fat and nanofat grafts. They had better histological structure and acted as scaffolds for adipogenesis and angiogenesis. Both products showed regenerative effects on dermal thickness; however, only lipoconcentrate grafts had the required volume and regenerative effects, allowing it to serve as a novel adipose-free grafting method for facial rejuvenation and contouring. NO LEVEL ASSIGNED This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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Affiliation(s)
- Vinh Vuong The Tran
- Department of Plastic and Reconstructive Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Ki Yong Hong
- Department of Plastic and Reconstructive Surgery, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Korea
| | - Xian Jin
- Department of Plastic and Reconstructive Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Hak Chang
- Department of Plastic and Reconstructive Surgery, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Korea.
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16
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Natsir Kalla DS, Alkaabi S, Fauzi A, Tajrin A, Nurrahma R, Müller WEG, Schröder HC, Wang X, Forouzanfar T, Helder MN, Ruslin M. Microfragmented Fat and Biphasic Calcium Phosphates for Alveolar Cleft Repair: Protocol for a Prospective, Nonblinded, First-in-Human Clinical Study. JMIR Res Protoc 2024; 13:e42371. [PMID: 38224475 PMCID: PMC10825761 DOI: 10.2196/42371] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2022] [Revised: 02/08/2023] [Accepted: 02/09/2023] [Indexed: 01/16/2024] Open
Abstract
BACKGROUND Biphasic calcium phosphates (BCP) may serve as off-the-shelf alternatives for iliac crest-derived autologous bone in alveolar cleft reconstructions. To add osteoinductivity to the osteoconductive BCPs to achieve similar regenerative capacity as autologous bone, a locally harvested buccal fat pad will be mechanically fractionated to generate microfragmented fat (MFAT), which has been shown to have high regenerative capacity due to high pericyte and mesenchymal stem cell content and a preserved perivascular niche. OBJECTIVE Our primary objectives will be to assess the feasibility and safety of the BCP-MFAT combination. The secondary objective will be efficacy, which will be evaluated using radiographic imaging and histological and histomorphometric evaluation of biopsies taken 6 months postoperatively, concomitant with dental implant placement. METHODS Eight patients with alveolar cleft (≥15 years) will be included in this prospective, nonblinded, first-in-human clinical study. MFAT will be prepared intraoperatively from the patient's own buccal fat pad. Regular blood tests and physical examinations will be conducted, and any adverse events (AEs) or serious EAs (SAEs) will be meticulously recorded. Radiographic imaging will be performed prior to surgery and at regular intervals after reconstruction of the alveolar cleft with the BCP-MFAT combination. Biopsies obtained after 6 months with a trephine drill used to prepare the implantation site will be assessed with histological and histomorphometric analyses after methylmethacrylate embedding and sectioning. RESULTS The primary outcome parameter will be safety after 6 months' follow-up, as monitored closely using possible occurrences of SAEs based on radiographic imaging, blood tests, and physical examinations. For efficacy, radiographic imaging will be used for clinical grading of the bone construct using the Bergland scale. In addition, bone parameters such as bone volume, osteoid volume, graft volume, and number of osteoclasts will be histomorphometrically quantified. Recruitment started in November 2019, and the trial is currently in the follow-up stage. This protocol's current version is 1.0, dated September 15, 2019. CONCLUSIONS In this first-in-human study, not only safety but also the histologically and radiographically assessed regenerative potential of the BCP-MFAT combination will be evaluated in an alveolar cleft model. When an SAE occurs, it will be concluded that the BCP-MFAT combination is not yet safe in the current setting. Regarding AEs, if they do not occur at a higher frequency than that in patients treated with standard care (autologous bone) or can be resolved by noninvasive conventional methods (eg, with analgesics or antibiotics), the BCP-MFAT combination will be considered safe. In all other cases, the BCP-MFAT combination will not yet be considered safe. TRIAL REGISTRATION Indonesia Clinical Trial Registry INA-EW74C1N; https://tinyurl.com/28tnrr64. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID) DERR1-10.2196/42371.
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Affiliation(s)
- Diandra Sabrina Natsir Kalla
- Department of Oral and Maxillofacial Surgery/Oral Pathology, Amsterdam University Medical Centers and Academic Centre for Dentistry Amsterdam, Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, Amsterdam, Netherlands
- Department of Biochemistry, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia
| | - Salem Alkaabi
- Department of Oral and Maxillofacial Surgery/Oral Pathology, Amsterdam University Medical Centers and Academic Centre for Dentistry Amsterdam, Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, Amsterdam, Netherlands
- Department of Oral and Maxillofacial Surgery, Fujairah Hospital, Ministry of Health, Fujairah, United Arab Emirates
| | - Abul Fauzi
- Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Hasanuddin University, Makassar, Indonesia
| | - Andi Tajrin
- Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Hasanuddin University, Makassar, Indonesia
| | - Rifaat Nurrahma
- Department of Oral and Maxillofacial Surgery/Oral Pathology, Amsterdam University Medical Centers and Academic Centre for Dentistry Amsterdam, Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, Amsterdam, Netherlands
- Department of Prosthodontics, Faculty of Dentistry, Hasanuddin University, Makassar, Indonesia
| | - Werner E G Müller
- ERC Advanced Investigator Grant Research Group at the Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, Mainz, Germany
| | - Heinz C Schröder
- ERC Advanced Investigator Grant Research Group at the Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, Mainz, Germany
| | - Xiaohong Wang
- ERC Advanced Investigator Grant Research Group at the Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, Mainz, Germany
| | - Tymour Forouzanfar
- Department of Oral and Maxillofacial Surgery/Oral Pathology, Amsterdam University Medical Centers and Academic Centre for Dentistry Amsterdam, Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, Amsterdam, Netherlands
- Department of Oral and Maxillofacial Surgery, Leiden University Medical Centre, Leiden, Netherlands
| | - Marco N Helder
- Department of Oral and Maxillofacial Surgery/Oral Pathology, Amsterdam University Medical Centers and Academic Centre for Dentistry Amsterdam, Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, Amsterdam, Netherlands
| | - Muhammad Ruslin
- Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Hasanuddin University, Makassar, Indonesia
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Limido E, Weinzierl A, Ampofo E, Harder Y, Menger MD, Laschke MW. Nanofat Accelerates and Improves the Vascularization, Lymphatic Drainage and Healing of Full-Thickness Murine Skin Wounds. Int J Mol Sci 2024; 25:851. [PMID: 38255932 PMCID: PMC10815416 DOI: 10.3390/ijms25020851] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2023] [Revised: 01/05/2024] [Accepted: 01/08/2024] [Indexed: 01/24/2024] Open
Abstract
The treatment of wounds using the body's own resources is a promising approach to support the physiological regenerative process. To advance this concept, we evaluated the effect of nanofat (NF) on wound healing. For this purpose, full-thickness skin defects were created in dorsal skinfold chambers of wild-type mice. These defects were filled with NF generated from the inguinal subcutaneous adipose tissue of green fluorescent protein (GFP)+ donor mice, which was stabilized using platelet-rich plasma (PRP). Empty wounds and wounds solely filled with PRP served as controls. Wound closure, vascularization and formation of granulation tissue were repeatedly analyzed using stereomicroscopy, intravital fluorescence microscopy, histology and immunohistochemistry over an observation period of 14 days. PRP + NF-treated wounds exhibited accelerated vascularization and wound closure when compared to controls. This was primarily due to the fact that the grafted NF contained a substantial fraction of viable GFP+ vascular and lymph vessel fragments, which interconnected with the GFP- vessels of the host tissue. Moreover, the switch from inflammatory M1- to regenerative M2-polarized macrophages was promoted in PRP + NF-treated wounds. These findings indicate that NF markedly accelerates and improves the wound healing process and, thus, represents a promising autologous product for future wound management.
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Affiliation(s)
- Ettore Limido
- Institute for Clinical and Experimental Surgery, Saarland University, 66421 Homburg, Germany; (E.L.); (A.W.); (E.A.); (M.D.M.)
| | - Andrea Weinzierl
- Institute for Clinical and Experimental Surgery, Saarland University, 66421 Homburg, Germany; (E.L.); (A.W.); (E.A.); (M.D.M.)
- Department of Plastic Surgery and Hand Surgery, University Hospital Zurich, 8091 Zurich, Switzerland
| | - Emmanuel Ampofo
- Institute for Clinical and Experimental Surgery, Saarland University, 66421 Homburg, Germany; (E.L.); (A.W.); (E.A.); (M.D.M.)
| | - Yves Harder
- Department of Plastic, Reconstructive and Aesthetic Surgery, Ospedale Regionale di Lugano, Ente Ospedaliero Cantonale (EOC), 6900 Lugano, Switzerland;
- Faculty of Biomedical Sciences, Università della Svizzera Italiana, 6900 Lugano, Switzerland
| | - Michael D. Menger
- Institute for Clinical and Experimental Surgery, Saarland University, 66421 Homburg, Germany; (E.L.); (A.W.); (E.A.); (M.D.M.)
| | - Matthias W. Laschke
- Institute for Clinical and Experimental Surgery, Saarland University, 66421 Homburg, Germany; (E.L.); (A.W.); (E.A.); (M.D.M.)
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18
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Malekzadeh H, Surucu Y, Chinnapaka S, Yang KS, Arellano JA, Samadi Y, Epperly MW, Greenberger JS, Rubin JP, Ejaz A. Metformin and adipose-derived stem cell combination therapy alleviates radiation-induced skin fibrosis in mice. Stem Cell Res Ther 2024; 15:13. [PMID: 38185658 PMCID: PMC10773046 DOI: 10.1186/s13287-023-03627-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2023] [Accepted: 12/26/2023] [Indexed: 01/09/2024] Open
Abstract
BACKGROUND Radiation therapy often leads to late radiation-induced skin fibrosis (RISF), causing movement impairment and discomfort. We conducted a comprehensive study to assess the effectiveness of metformin and adipose-derived stem cells (ASCs), whether autologous or allogeneic, individually or in combination therapy, in mitigating RISF. METHODS Using a female C57BL/6J mouse model subjected to hind limb irradiation as a representative RISF model, we evaluated metformin, ASCs, or their combination in two contexts: prophylactic (started on day 1 post-irradiation) and therapeutic (initiated on day 14 post-irradiation, coinciding with fibrosis symptoms). We measured limb movement, examined skin histology, and analyzed gene expression to assess treatment efficacy. RESULTS Prophylactic metformin and ASCs, whether autologous or allogeneic, effectively prevented late fibrosis, with metformin showing promising results. However, combination therapy did not provide additional benefits when used prophylactically. Autologous ASCs, alone or with metformin, proved most effective against late-stage RISF. Prophylactic intervention outperformed late therapy for mitigating radiation skin damage. Co-culture studies revealed that ASCs and metformin downregulated inflammation and fibrotic gene expression in both mouse and human fibroblasts. CONCLUSIONS Our study suggests metformin's potential as a prophylactic measure to prevent RISF, and the combination of ASCs and metformin holds promise for late-stage RISF treatment. These findings have clinical implications for improving the quality of life for those affected by radiation-induced skin fibrosis.
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Affiliation(s)
- Hamid Malekzadeh
- Department of Plastic Surgery, University of Pittsburgh Medical Center, 3550 Terrace Street, 6B Scaife Hall, Pittsburgh, PA, 15261, USA
| | - Yusuf Surucu
- Department of Plastic Surgery, University of Pittsburgh Medical Center, 3550 Terrace Street, 6B Scaife Hall, Pittsburgh, PA, 15261, USA
| | - Somaiah Chinnapaka
- Department of Plastic Surgery, University of Pittsburgh Medical Center, 3550 Terrace Street, 6B Scaife Hall, Pittsburgh, PA, 15261, USA
| | - Katherine S Yang
- Department of Plastic Surgery, University of Pittsburgh Medical Center, 3550 Terrace Street, 6B Scaife Hall, Pittsburgh, PA, 15261, USA
| | - José A Arellano
- Department of Plastic Surgery, University of Pittsburgh Medical Center, 3550 Terrace Street, 6B Scaife Hall, Pittsburgh, PA, 15261, USA
| | - Yasamin Samadi
- Department of Plastic Surgery, University of Pittsburgh Medical Center, 3550 Terrace Street, 6B Scaife Hall, Pittsburgh, PA, 15261, USA
| | - Michael W Epperly
- Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA
| | - Joel S Greenberger
- Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA
| | - J Peter Rubin
- Department of Plastic Surgery, University of Pittsburgh Medical Center, 3550 Terrace Street, 6B Scaife Hall, Pittsburgh, PA, 15261, USA
- McGowan Institute, University of Pittsburgh, Pittsburgh, USA
- Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, USA
| | - Asim Ejaz
- Department of Plastic Surgery, University of Pittsburgh Medical Center, 3550 Terrace Street, 6B Scaife Hall, Pittsburgh, PA, 15261, USA.
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19
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Eremin II, Vasiliev VS, Tikhomirov AN, Chibizov PE, Briko AN, Kotenko KV. [Experimental substantiation of medical device design for mechanical processing of adipose tissue]. Khirurgiia (Mosk) 2024:101-108. [PMID: 39665353 DOI: 10.17116/hirurgia2024122101] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2024]
Abstract
OBJECTIVE To substantiate the medical device design for mechanical processing of adipose tissue. MATERIAL AND METHODS Enzymatic method using collagenase and mechanical method for obtaining the stromal vascular fraction (SVF) are compared. The authors emphasized the disadvantages of enzymatic method, such as high cost and duration of process. The main criteria for developing the design were cell viability after processing of adipose tissue and available processing in a minimum number of passages manually without automated mechanical stands. RESULTS The proposed design allows two unidirectional passages to obtain processed lipoaspirate for SVF harvesting. Experimental studies demonstrate that meshes with a minimum cell size of 100 μm allow high cell viability comparable to enzymatic method. Moreover, this design can be used to develop a disposable medical device. CONCLUSION Our results will underlie development of a disposable medical device for mechanical processing of adipose tissue.
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Affiliation(s)
- I I Eremin
- Petrovsky National Research Center of Surgery, Moscow, Russia
| | - V S Vasiliev
- Institute of Plastic Surgery and Cosmetology, Moscow, Russia
| | - A N Tikhomirov
- Bauman Moscow State Technical University, Moscow, Russia
| | - P E Chibizov
- Bauman Moscow State Technical University, Moscow, Russia
| | - A N Briko
- Petrovsky National Research Center of Surgery, Moscow, Russia
| | - K V Kotenko
- Petrovsky National Research Center of Surgery, Moscow, Russia
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20
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Sun Y, Wu G, Dai T, Li S, Cao W, Dai T. Stromal Vascular Fraction Gel (SVF-Gel) Combined with Nanofat for Tear Trough Deformity. Aesthetic Plast Surg 2024; 48:213-220. [PMID: 37957391 DOI: 10.1007/s00266-023-03698-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Accepted: 09/20/2023] [Indexed: 11/15/2023]
Abstract
BACKGROUND Tear trough deformity makes patients appear tired. Patients with less severe tear trough deformity prefer a less invasive method to correct the deformity. The infraorbital area is a multilayered tissue, and the aging of various components leads to tear trough deformity. To this end, we utilized the different characteristics of different fat derivatives to correct tear trough deformity. METHODS Thirty-two patients with Barton Grade I/II tear trough deformity were enrolled in this study between September 2020 and March 2021. We injected Stromal Vascular Fraction Gel (SVF-Gel) into the suborbicularis oculi fat layer and Nanofat into the subcutaneous. After 12 months of follow-up, we evaluated the changes using standardized clinical photogrammetric techniques, volume, global aesthetic improvement scale, and patient self-evaluation. RESULTS There were no major complications in any of the 32 patients. The measured data points demonstrated improvements in all aesthetic parameters. The width of the tear trough and the distance from the pupil to the tear trough improved. The Global Aesthetic Improvement Scale (GAIS) showed a high score (2.45±0.64 points), with patient self-assessment showing satisfactory results. CONCLUSION SVF-Gel combined with Nanofat injection can effectively correct tear trough deformities. LEVEL OF EVIDENCE IV This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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Affiliation(s)
- Yiyu Sun
- Department of Wound Reconstructive Surgery, Tongji Hospital, Tongji University, Shanghai, China
| | - Gaoyang Wu
- Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhi Zao Ju Road, Shanghai, China
| | - Tao Dai
- Department of Wound Reconstructive Surgery, Tongji Hospital, Tongji University, Shanghai, China
| | - Shengli Li
- Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhi Zao Ju Road, Shanghai, China
| | - Weigang Cao
- Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhi Zao Ju Road, Shanghai, China.
| | - Tingting Dai
- Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhi Zao Ju Road, Shanghai, China.
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21
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Veronesi F, Andriolo L, Salerno M, Boffa A, Giavaresi G, Filardo G. Adipose Tissue-Derived Minimally Manipulated Products versus Platelet-Rich Plasma for the Treatment of Knee Osteoarthritis: A Systematic Review of Clinical Evidence and Meta-Analysis. J Clin Med 2023; 13:67. [PMID: 38202074 PMCID: PMC10780289 DOI: 10.3390/jcm13010067] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2023] [Revised: 12/07/2023] [Accepted: 12/14/2023] [Indexed: 01/12/2024] Open
Abstract
The use of minimally manipulated adipose tissue (MM-AT) products is gaining increasing interest for the treatment of knee osteoarthritis (OA). MM-AT represents an easy way to exploit adipose tissue properties, although clinical evidence is still limited, as well as their benefits with respect to more documented orthobiologics like platelet-rich plasma (PRP). A systematic review and meta-analysis were performed to evaluate the safety and efficacy of MM-AT products for knee OA management. The risk of bias of the included studies was evaluated using the Dawns and Black checklist for all the included studies and RoB-2.0 for randomized controlled trials (RCTs). Thirty-three clinical studies were included in the qualitative analysis: 13 prospective case series, 10 retrospective case series, 7 RCTs, 2 retrospective comparative studies, and 1 prospective comparative study. An overall clinical improvement and few minor adverse events were observed. Five RCTs comparing MM-AT and PRP injections were meta-analyzed, showing comparable results. The analysis also highlighted the limits of the literature, with only a few high-level trials and an overall low quality. Even though the current literature is still limited, the available evidence suggests the safety and overall positive results of the intra-articular injections of MM-AT products for knee OA treatment.
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Affiliation(s)
- Francesca Veronesi
- Surgical Sciences and Technologies, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy; (F.V.); (G.G.)
| | - Luca Andriolo
- Clinica Ortopedica e Traumatologica 2, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy;
| | - Manuela Salerno
- Applied and Translational Research (ATR) Center, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy; (M.S.)
| | - Angelo Boffa
- Clinica Ortopedica e Traumatologica 2, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy;
| | - Gianluca Giavaresi
- Surgical Sciences and Technologies, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy; (F.V.); (G.G.)
| | - Giuseppe Filardo
- Applied and Translational Research (ATR) Center, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy; (M.S.)
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22
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Liu M, Lu F, Feng J. Therapeutic potential of adipose tissue derivatives in skin photoaging. Regen Med 2023; 18:869-883. [PMID: 37743749 DOI: 10.2217/rme-2023-0098] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/26/2023] Open
Abstract
Photoaging, the primary cause of exogenous skin aging and predominantly caused by ultraviolet radiation, is an essential type of skin aging characterized by chronic skin inflammation. Recent studies have shown that oxidative stress, inflammation, skin barrier homeostasis, collagen denaturation and pigmentation are the main contributors to it. As a composite tissue rich in matrix and vascular components, adipose tissue derivatives have been recently gaining attention as potential therapeutic agents for various human diseases with fat-processing technology upgrades. This review analyzes both 'minimally treated' and 'nonminimally treated' fat derivatives to give an overview of the preclinical and clinical relevance of adipose tissue derivatives for antiphotoaging application, highlighting their good clinical prospects as well as discussing their safety and potential risks.
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Affiliation(s)
- Meiqi Liu
- Department of Plastic & Cosmetic Surgery, Nanfang Hospital, Southern Medical University, 1838 Guangzhou North Road, Guangzhou, Guangdong 510515, PR China
| | - Feng Lu
- Department of Plastic & Cosmetic Surgery, Nanfang Hospital, Southern Medical University, 1838 Guangzhou North Road, Guangzhou, Guangdong 510515, PR China
| | - Jingwei Feng
- Department of Plastic & Cosmetic Surgery, Nanfang Hospital, Southern Medical University, 1838 Guangzhou North Road, Guangzhou, Guangdong 510515, PR China
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23
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Wu V, Klein-Nulend J, Bravenboer N, ten Bruggenkate CM, Helder MN, Schulten EAJM. Long-Term Safety of Bone Regeneration Using Autologous Stromal Vascular Fraction and Calcium Phosphate Ceramics: A 10-Year Prospective Cohort Study. Stem Cells Transl Med 2023; 12:617-630. [PMID: 37527504 PMCID: PMC10502529 DOI: 10.1093/stcltm/szad045] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2023] [Accepted: 07/04/2023] [Indexed: 08/03/2023] Open
Abstract
This prospective cohort study aimed to assess long-term safety, dental implant survival, and clinical and radiological outcomes after maxillary sinus floor elevation (MSFE; lateral window technique) using freshly isolated autologous stromal vascular fraction (SVF) combined with calcium phosphate ceramics. All 10 patients previously participating in a phase I trial were included in a 10-year follow-up. They received either β-tricalcium phosphate (β-TCP; n = 5) or biphasic calcium phosphate (BCP; n = 5) with SVF-supplementation on one side (study). Bilaterally treated patients (6 of 10; 3 β-TCP, 3 BCP) received only calcium phosphate on the opposite side (control). Clinical and radiological assessments were performed on 44 dental implants at 1-month pre-MSFE, and 0.5- to 10-year post-MSFE. Implants were placed 6 months post-MSFE. No adverse events or pathology was reported during a 10-year follow-up. Forty-three dental implants (98%) remained functional. Control and study sides showed similar peri-implant soft-tissue quality, sulcus bleeding index, probing depth, plaque index, keratinized mucosa width, as well as marginal bone loss (0-6 mm), graft height loss (0-6 mm), and graft volume reduction. Peri-implantitis was observed around 6 implants (control: 4; study: 2) in 3 patients. This study is the first to demonstrate the 10-year safety of SVF-supplementation in MSFE for jawbone reconstruction. SVF-supplementation showed enhanced bone regeneration in the short term (previous study) and led to no abnormalities clinically and radiologically in the long term.
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Affiliation(s)
- Vivian Wu
- Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, Amsterdam, The Netherlands
- Department of Oral and Maxillofacial Surgery/Oral Pathology, Amsterdam UMC and Academic Centre for Dentistry Amsterdam (ACTA), Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, Amsterdam, The Netherlands
| | - Jenneke Klein-Nulend
- Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, Amsterdam, The Netherlands
| | - Nathalie Bravenboer
- Department of Clinical Chemistry, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, Amsterdam, The Netherlands
| | - Christiaan M ten Bruggenkate
- Department of Oral and Maxillofacial Surgery/Oral Pathology, Amsterdam UMC and Academic Centre for Dentistry Amsterdam (ACTA), Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, Amsterdam, The Netherlands
| | - Marco N Helder
- Department of Oral and Maxillofacial Surgery/Oral Pathology, Amsterdam UMC and Academic Centre for Dentistry Amsterdam (ACTA), Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, Amsterdam, The Netherlands
| | - Engelbert A J M Schulten
- Department of Oral and Maxillofacial Surgery/Oral Pathology, Amsterdam UMC and Academic Centre for Dentistry Amsterdam (ACTA), Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, Amsterdam, The Netherlands
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24
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Lau CS, Chua J, Prasadh S, Lim J, Saigo L, Goh BT. Alveolar Ridge Augmentation with a Novel Combination of 3D-Printed Scaffolds and Adipose-Derived Mesenchymal Stem Cells-A Pilot Study in Pigs. Biomedicines 2023; 11:2274. [PMID: 37626770 PMCID: PMC10452669 DOI: 10.3390/biomedicines11082274] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Revised: 08/01/2023] [Accepted: 08/10/2023] [Indexed: 08/27/2023] Open
Abstract
Alveolar ridge augmentation is an important dental procedure to increase the volume of bone tissue in the alveolar ridge before the installation of a dental implant. To meet the high demand for bone grafts for alveolar ridge augmentation and to overcome the limitations of autogenous bone, allografts, and xenografts, researchers are developing bone grafts from synthetic materials using novel fabrication techniques such as 3D printing. To improve the clinical performance of synthetic bone grafts, stem cells with osteogenic differentiation capability can be loaded into the grafts. In this pilot study, we propose a novel bone graft which combines a 3D-printed polycaprolactone-tricalcium phosphate (PCL-TCP) scaffold with adipose-derived mesenchymal stem cells (AD-MSCs) that can be harvested, processed and implanted within the alveolar ridge augmentation surgery. We evaluated the novel bone graft in a porcine lateral alveolar defect model. Radiographic analysis revealed that the addition of AD-MSCs to the PCL-TCP scaffold improved the bone volume in the defect from 18.6% to 28.7% after 3 months of healing. Histological analysis showed the presence of AD-MSCs in the PCL-TCP scaffold led to better formation of new bone and less likelihood of fibrous encapsulation of the scaffold. Our pilot study demonstrated that the loading of AD-MSCs improved the bone regeneration capability of PCL-TCP scaffolds, and our novel bone graft is suitable for alveolar ridge augmentation.
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Affiliation(s)
- Chau Sang Lau
- National Dental Research Institute Singapore, National Dental Centre Singapore, Singapore 168938, Singapore; (C.S.L.); (L.S.)
- Oral Health Academic Clinical Programme, Duke-NUS Medical School, Singapore 169857, Singapore
| | - Jasper Chua
- Duke-NUS Medical School, Singapore 169857, Singapore;
| | - Somasundaram Prasadh
- Center for Clean Energy Engineering, University of Connecticut, Storrs, CT 06269, USA;
| | - Jing Lim
- Osteopore International Pte Ltd., Singapore 618305, Singapore;
| | - Leonardo Saigo
- National Dental Research Institute Singapore, National Dental Centre Singapore, Singapore 168938, Singapore; (C.S.L.); (L.S.)
| | - Bee Tin Goh
- National Dental Research Institute Singapore, National Dental Centre Singapore, Singapore 168938, Singapore; (C.S.L.); (L.S.)
- Oral Health Academic Clinical Programme, Duke-NUS Medical School, Singapore 169857, Singapore
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25
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Lim YC, Jung JI, Hong IK. A Novel Method for Human Adipose-Derived Stem Cell Isolation and Cryopreservation. Cell Reprogram 2023; 25:171-179. [PMID: 37590008 DOI: 10.1089/cell.2023.0017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/18/2023] Open
Abstract
Adipose-derived stem cells (ADSCs) are isolated from abundant adipose tissue and have the capacity to differentiate into multiple cell lineages. ADSCs have raised big interest in therapeutic applications in regenerative medicine and demonstrated to fulfill the criteria for a successful cell therapy. There are several methods for isolation of ADSCs from adipose tissue and cryopreservation of ADSCs. Here, novel methods for the isolation and cryopreservation of ADSCs are presented and focused. Microscopic pieces of adipose tissue were placed on transwell inserts, and the ADSCs were induced to migrate to the lower wells for 1 week. We compared the properties of our ADSCs with those isolated by enzymatic digestion and enzyme-free method of culture plate, and our ADSCs were found to be more stable and healthier. In addition, we proposed a novel cryoprotectant solution (FNCP) containing pectin and L-alanine, which was compared with standard cryoprotectant solution. Overall, our methods proved more useful for ADSCs isolation than other methods and did not require consideration of "minimal manipulation" by the U.S. Food and Drug Administration (FDA). Furthermore, our FNCP did not contain dimethyl sulfoxide and fetal bovine serum, therefore stable storage is possible in xeno-free and animal-free cryopreservation solutions.
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Affiliation(s)
- Young-Cheol Lim
- Bio Lab. Efficacy Research Team, Frombio. Co., Ltd, Yongin-si, Republic of Korea
| | - Jung-Il Jung
- Bio Lab. Efficacy Research Team, Frombio. Co., Ltd, Yongin-si, Republic of Korea
| | - In-Kee Hong
- Bio Lab. Efficacy Research Team, Frombio. Co., Ltd, Yongin-si, Republic of Korea
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26
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Pennasilico L, Di Bella C, Sassaroli S, Salvaggio A, Roggiolani F, Piccionello AP. Effects of Autologous Microfragmented Adipose Tissue on Healing of Tibial Plateau Levelling Osteotomies in Dogs: A Prospective Clinical Trial. Animals (Basel) 2023; 13:2084. [PMID: 37443881 DOI: 10.3390/ani13132084] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2023] [Revised: 06/20/2023] [Accepted: 06/21/2023] [Indexed: 07/15/2023] Open
Abstract
The aim of this study was to evaluate the effects of autologous microfragmented adipose tissue (MFAT) applied after mechanical fragmentation and assess these effects radiographically in bone healing in dogs subjected to tibial plateau levelling osteotomy (TPLO). Twenty dogs with unilateral cranial cruciate ligament disease were enrolled and randomly assigned to the treatment group (MFAT) or the control group (NT). The MFAT group underwent TPLO and autologous MFAT intra-articular administration, while the NT group underwent TPLO alone. Adipose tissue was collected from the thigh region, and MFAT was obtained by mechanical fragmentation at the end of the surgery. The patients were subjected to X-ray examination preoperatively, immediately postoperatively (T0), and at 4 (T1) and 8 (T2) weeks postoperatively. Two radiographic scores that had previously been described for the evaluation of bone healing after TPLO were used. A 12-point scoring system (from 0 = no healing to 12 = complete remodelling) was used at T0, T1, and T2, while a 5-point scoring system (from 0 = no healing to 4 = 76-100% of healing) was used at T1 and T2. The median healing scores were significantly higher at T1 and T2 for the MFAT group compared with the NT group for the 12-point (p < 0.05) and 5-point (p < 0.05) scoring systems. The intra-articular injection of autologous microfragmented adipose tissue can accelerate bone healing after TPLO without complications.
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Affiliation(s)
- Luca Pennasilico
- School of Bioscience and Veterinary Medicine, University of Camerino, 62024 Matelica, Italy
| | - Caterina Di Bella
- School of Bioscience and Veterinary Medicine, University of Camerino, 62024 Matelica, Italy
| | - Sara Sassaroli
- School of Bioscience and Veterinary Medicine, University of Camerino, 62024 Matelica, Italy
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27
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G. Ryabkov M, N. Egorikhina M, A. Koloshein N, S. Petrova K, G. Volovik M, Yu. Orlinskaya N, O. Moskovchenko A, N. Charykova I, Ya. Aleynik D, D. Linkova D, E. Pogodin I, I. Kobyakova I, Yu. Arefyev I. Effectiveness and Safety of Transplantation of the Stromal Vascular Fraction of Autologous Adipose Tissue for Wound Healing in the Donor Site in Patients with Third-Degree Skin Burns: A Randomized Trial. Med J Islam Repub Iran 2023; 37:70. [PMID: 37575690 PMCID: PMC10423061 DOI: 10.47176/mjiri.37.70] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Indexed: 08/15/2023] Open
Abstract
Background The quality of the wound healing at the donor site significantly determines the overall condition of the burn patient, the extent of wound fluid and protein losses, the severity of any systemic in-flammatory reaction, and the intensity of the pain syndrome. It is known that the stromal vas-cular fraction (SVF) has a beneficial effect on the healing of wound defects. This study is aimed at assessing the safety and effectiveness of the application of the SVF of autologous adipose tis-sue to stimulate wound healing of the donor site in patients with burns. Methods This placebo-controlled clinical study included 38 patients with third-degree thermal skin burns. The patients underwent liposuction, enzymatic isolation of the SVF, and intradermal injection of the preparation into the wounds in the donor site, followed by tewametry, cutome-try, thermography and biopsy after 12 days. Quantitative indicators were compared using the Mann-Whitney test for unrelated groups and the Wilcoxon test for related groups. Spearman's rank correlation coefficient (RS) was used to assess the correlation. Results Epithelization of the wounds in all patients was seen over an average area of 88 (84;92) %, there being no significant differences between the actual and the control wound sites for this parameter. Transdermal water loss in the test wound sites was 2 times lower than in the control sites (P = 0.001). The wound donor sites regained their temperature distribution faster than the control sites (P = 0.042). Histological preparations of the skin of the wound sites revealed that their epidermal layer was 19% thicker compared to the controls (P = 0.043). It should be noted that five adverse events related to manipulations in the postoperative period were registered. Conclusion Transplantation of SVF autologous adipose tissue into the wound area in most clinical cases proceeded without complications. The area of epithelialization of wound areas af-ter the introduction of SVF did not change, although a significant decrease in transdermal water loss was observed in the wound areas with an improvement in their thermoregulation and an increase in the thickness of the epidermis.
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Affiliation(s)
- Maksim G. Ryabkov
- Federal State Budgetary Educational Institution of Higher Education Privolzhsky Research Medical University of the Ministry of Health of the Russian Federation, 603005 Nizhny Novgorod, Russia
| | - Marfa N. Egorikhina
- Federal State Budgetary Educational Institution of Higher Education Privolzhsky Research Medical University of the Ministry of Health of the Russian Federation, 603005 Nizhny Novgorod, Russia
| | - Nikita A. Koloshein
- Federal State Budgetary Educational Institution of Higher Education Privolzhsky Research Medical University of the Ministry of Health of the Russian Federation, 603005 Nizhny Novgorod, Russia
| | - Kseniya S. Petrova
- Federal State Budgetary Educational Institution of Higher Education Privolzhsky Research Medical University of the Ministry of Health of the Russian Federation, 603005 Nizhny Novgorod, Russia
| | - Mikhail G. Volovik
- Federal State Budgetary Educational Institution of Higher Education Privolzhsky Research Medical University of the Ministry of Health of the Russian Federation, 603005 Nizhny Novgorod, Russia
| | - Nataliya Yu. Orlinskaya
- Federal State Budgetary Educational Institution of Higher Education Privolzhsky Research Medical University of the Ministry of Health of the Russian Federation, 603005 Nizhny Novgorod, Russia
| | - Aleksandra O. Moskovchenko
- Federal State Budgetary Educational Institution of Higher Education Privolzhsky Research Medical University of the Ministry of Health of the Russian Federation, 603005 Nizhny Novgorod, Russia
| | - Irina N. Charykova
- Federal State Budgetary Educational Institution of Higher Education Privolzhsky Research Medical University of the Ministry of Health of the Russian Federation, 603005 Nizhny Novgorod, Russia
| | - Diana Ya. Aleynik
- Federal State Budgetary Educational Institution of Higher Education Privolzhsky Research Medical University of the Ministry of Health of the Russian Federation, 603005 Nizhny Novgorod, Russia
| | - Daria D. Linkova
- Federal State Budgetary Educational Institution of Higher Education Privolzhsky Research Medical University of the Ministry of Health of the Russian Federation, 603005 Nizhny Novgorod, Russia
| | - Igor E. Pogodin
- Federal State Budgetary Educational Institution of Higher Education Privolzhsky Research Medical University of the Ministry of Health of the Russian Federation, 603005 Nizhny Novgorod, Russia
| | - Irina I. Kobyakova
- Federal State Budgetary Educational Institution of Higher Education Privolzhsky Research Medical University of the Ministry of Health of the Russian Federation, 603005 Nizhny Novgorod, Russia
| | - Igor Yu. Arefyev
- Federal State Budgetary Educational Institution of Higher Education Privolzhsky Research Medical University of the Ministry of Health of the Russian Federation, 603005 Nizhny Novgorod, Russia
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Semenzato M, Zambello L, Fumarola S, Motta E, Piroli L, Scorrano L, Bean C. A Novel Benchtop Device for Efficient and Simple Purification of Cytokines, Growth Factors and Stem Cells from Adipose Tissue. Biomedicines 2023; 11:biomedicines11041006. [PMID: 37189624 DOI: 10.3390/biomedicines11041006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Revised: 03/17/2023] [Accepted: 03/22/2023] [Indexed: 05/17/2023] Open
Abstract
Lipoaspirates represent a source of adult stem cells, cytokines, and growth factors of adipocyte origin with immunomodulation and regenerative medicine potential. However, rapid and simple protocols for their purification using self-contained devices that can be deployed at the points of care are lacking. Here, we characterize and benchmark a straightforward mechanical dissociation procedure to collect mesenchymal stem cells (MSCs) and soluble fractions from lipoaspirates. IStemRewind, a benchtop self-contained cell purification device, allowed a one-procedure purification of cells and soluble material from lipoaspirates with minimal manipulation. The recovered cellular fraction contained CD73+, CD90+, CD105+, CD10+ and CD13+ MSCs. These markers were comparably expressed on MSCs isolated using IstemRewind or classic enzymatic dissociation procedures, apart from CD73+ MSCs, which were even more abundant in IStemRewind isolates. IstemRewind-purified MSCs retained viability and differentiation into adipocytes and osteocytes, even after a freezing-thawing cycle. Levels of IL4, IL10, bFGF and VEGF were higher compared to the pro-inflammatory cytokines TNFα, IL1β and IL6 in the IStemRewind-isolated liquid fraction. In sum, IStemRewind can be useful for straightforward, rapid, and efficient isolation of MSCs and immunomodulatory soluble factors from lipoaspirates, opening the possibility to directly isolate and employ them at the point-of-care.
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Affiliation(s)
- Martina Semenzato
- Department of Biology, University of Padova, Via U.Bassi 58/B, 35121 Padova, Italy
- Veneto Institute of Molecular Medicine, 35129 Padova, Italy
| | - Ludovica Zambello
- Department of Biology, University of Padova, Via U.Bassi 58/B, 35121 Padova, Italy
- Veneto Institute of Molecular Medicine, 35129 Padova, Italy
| | - Stefania Fumarola
- InScientiaFides Foundation, Strada di Paderna, 2, 47895 San Marino, San Marino
| | | | - Luana Piroli
- InScientiaFides Foundation, Strada di Paderna, 2, 47895 San Marino, San Marino
| | - Luca Scorrano
- Department of Biology, University of Padova, Via U.Bassi 58/B, 35121 Padova, Italy
- Veneto Institute of Molecular Medicine, 35129 Padova, Italy
| | - Camilla Bean
- Veneto Institute of Molecular Medicine, 35129 Padova, Italy
- Department of Medicine, University of Udine, Piazzale Kolbe 4, 33100 Udine, Italy
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Bohlouli M, Bastami F, Nokhbatolfoghahei H, Khojasteh A. Tissue buccal fat pad-stromal vascular fraction as a safe source in maxillofacial bone regeneration: A clinical pilot study. J Plast Reconstr Aesthet Surg 2023; 79:111-121. [PMID: 36917913 DOI: 10.1016/j.bjps.2023.01.027] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2022] [Revised: 11/24/2022] [Accepted: 01/29/2023] [Indexed: 02/09/2023]
Abstract
AIM The purpose of this study was to examine the biological properties of the buccal fat pad (BFP)-derived tissue stromal vascular fraction (tSVF) in vitro and compare them with BFP-derived cellular SVF (cSVF). Furthermore, a clinical pilot study assessed the safety of using BFP-derived tSVF for maxillofacial bone regeneration. MATERIALS AND METHODS This study was performed in two sections: 1) experimental section: BFP tissue was harvested from three healthy donors, and then cSVF and tSVF were isolated by enzymatic and mechanical methods to assess their biological properties and 2) clinical section: Ten patients with maxillofacial bone defects were enrolled according to eligibility criteria and offered two options for surgery, including autologous BFP-tSVF (n = 5) and autologous bone grafting (n = 5), to evaluate safety after a year of follow-up. RESULTS The BFP-tSVF exhibited high cell viability and various cell surface markers, including CD45, CD31, and CD34. There was no population-doubling time and multilineage differentiation capacity compared with BFP-cSVF. BFP-tSVF is safe because of the lack of intervention-related adverse events reported in donor and surgery sites during a one-year period. In addition, cell therapy was feasible because it can be performed during surgery and requires little preparation time. Patients in the ABG group experienced pain and tenderness in the iliac crest, leading to dissatisfaction and complications. CONCLUSION The experimental results confirmed that the cells isolated from BFP-tSVF have stemness properties similar to BFP-cSVF. Clinical evaluation also indicated that this cellular product could be used safely to regenerate maxillofacial bone defects.
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Affiliation(s)
- Mahboubeh Bohlouli
- Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Fashid Bastami
- Department of Oral-Maxillofacial Surgery, Dental Research Center, Research Institute of Dental Sciences Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hanieh Nokhbatolfoghahei
- Dental Research Center, Research Institute of Dental Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Arash Khojasteh
- Dental Research Center, Research Institute of Dental Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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Cheng HY, Anggelia MR, Lin CH, Wei FC. Toward transplantation tolerance with adipose tissue-derived therapeutics. Front Immunol 2023; 14:1111813. [PMID: 37187733 PMCID: PMC10175575 DOI: 10.3389/fimmu.2023.1111813] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Accepted: 04/07/2023] [Indexed: 05/17/2023] Open
Abstract
Solid organ and composite tissue allotransplanation have been widely applied to treat end-stage organ failure and massive tissue defects, respectively. Currently there are a lot of research endeavors focusing on induction of transplantation tolerance, to relieve the burden derived from long-term immunosuppressant uptake. The mesenchymal stromal cells (MSCs) have been demonstrated with potent immunomodulatory capacities and applied as promising cellular therapeutics to promote allograft survival and induce tolerance. As a rich source of adult MSCs, adipose tissue provides additional advantages of easy accessibility and good safety profile. In recent years, the stromal vascular fraction (SVF) isolated from adipose tissues following enzymatic or mechanical processing without in vitro culture and expansion has demonstrated immunomodulatory and proangiogenic properties. Furthermore, the secretome of AD-MSCs has been utilized in transplantation field as a potential "cell-free" therapeutics. This article reviews recent studies that employ these adipose-derived therapeutics, including AD-MSCs, SVF, and secretome, in various aspects of organ and tissue allotransplantation. Most reports validate their efficacies in prolonging allograft survival. Specifically, the SVF and secretome have performed well for graft preservation and pretreatment, potentially through their proangiogenic and antioxidative capacities. In contrast, AD-MSCs were suitable for peri-transplantation immunosuppression. The proper combination of AD-MSCs, lymphodepletion and conventional immunosuppressants could consistently induce donor-specific tolerance to vascularized composite allotransplants (VCA). For each type of transplantation, optimizing the choice of therapeutics, timing, dose, and frequency of administration may be required. Future progress in the application of adipose-derived therapeutics to induce transplantation tolerance will be further benefited by continued research into their mechanisms of action and the development of standardized protocols for isolation methodologies, cell culture, and efficacy evaluation.
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Affiliation(s)
- Hui-Yun Cheng
- Center for Vascularized Composite Allotransplantation, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
- *Correspondence: Hui-Yun Cheng,
| | - Madonna Rica Anggelia
- Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
| | - Cheng-Hung Lin
- Center for Vascularized Composite Allotransplantation, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
- Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
- School of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Fu-Chan Wei
- Center for Vascularized Composite Allotransplantation, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
- Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
- School of Medicine, Chang Gung University, Taoyuan, Taiwan
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Hybrid Stromal Vascular Fraction (Hybrid-SVF): A New Paradigm in Mechanical Regenerative Cell Processing. Plast Reconstr Surg Glob Open 2022; 10:e4702. [PMID: 36601591 PMCID: PMC9803457 DOI: 10.1097/gox.0000000000004702] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Accepted: 10/11/2022] [Indexed: 01/06/2023]
Abstract
Enzymatic digestion of extracellular matrix (ECM) from lipoaspirate is the conventional form of harvesting stromal vascular fraction (SVF) called enzymatically digested SVF (E-SVF). Mechanical SVF (M-SVF) isolation has emerged as an alternative method, but it has also some limitations in terms of lower cell viability and diminished cell counts. To enhance the SVF qualitatively and quantitatively, we propose a novel concept called "hybrid-SVF," in which we combine M-SVF with the concentrated parts of adipose tissue after centrifugation, which is called stromal vascular matrix (SVM). Methods Hybrid-SVF injection was applied as an adjunctive therapy to fat grafting in 88 patients and 11 samples were evaluated in the laboratory for cell count, viability and cell activity. Results Experimental results determined that SVM part showed higher cellular activity. SVM and M-SVF showed higher cellular potency than E-SVF. Clinically, none of the patients required an additional session for fat grafting since there was no significant graft resorption. However, seven patients asked for further volume augmentation due to their individual preferences. No major complication was encountered. Conclusions The usage of hybrid-SVF has a very high regenerative potential due to the ECM support and exceptionally high cell yield in addition to preserved cell potency. Although there are ongoing studies focusing on optimizing cell counts and further clinical applications, we believe that our preliminary results might create a paradigm shift in the area of regenerative fat grafting.
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Chen W, He Z, Li S, Wu Z, Tan J, Yang W, Li G, Pan X, Liu Y, Lyu FJ, Li W. The Effect of Tissue Stromal Vascular Fraction as Compared to Cellular Stromal Vascular Fraction to Treat Anal Sphincter Incontinence. BIOENGINEERING (BASEL, SWITZERLAND) 2022; 10:bioengineering10010032. [PMID: 36671604 PMCID: PMC9854502 DOI: 10.3390/bioengineering10010032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/17/2022] [Revised: 11/30/2022] [Accepted: 12/12/2022] [Indexed: 12/28/2022]
Abstract
BACKGROUND The long-term prognosis of current treatments for anal sphincter incontinence (ASI) is poor. Here, we explored the efficacy of tissue adipose stromal vascular fraction SVF (tSVF) on ASI and compared it to that of cellular SVF (cSVF). We then investigated possible mechanisms. METHODS Rat cSVF and tSVF were isolated and labeled with DIL. One day after modeling, three groups received phosphate-buffered saline (PBS), cSVF, tSVF, respectively. The control group received nil modeling nor any treatments. The effect was assessed by function test for anal pressure and electromyography, and staining for fiber content, proliferation and differentiation at day 5 and day 10. RESULTS cSVF injection resulted in faster healing than tSVF. The cSVF group showed significant improvement on anal pressure on day 10. For the electromyography test, cSVF showed significant improvement for the frequencies on day 10, and for the peak values on both time points, while tSVF showed significant improvement for the peak values on day 10. The two SVF both alleviated fibrosis. Immunofluorescence tracing identified differentiation of some injected cells towards myosatellite cells and smooth muscle cells in both SVF groups. For all the tests, the tSVF group tends to have similar or lower effects than the cSVF group with no significant difference. CONCLUSION cSVF and tSVF are both safe and effective in treating ASI, while the effect of cSVF is slighter higher than tSVF.
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Affiliation(s)
- Wenbin Chen
- Department of Colorectal and Anal Surgery, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou 510641, China
| | - Zijian He
- Department of Colorectal and Anal Surgery, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou 510641, China
| | - Shuyu Li
- School of Biology and Biological Engineering, South China University of Technology, Guangzhou 510641, China
| | - Zixin Wu
- Department of Colorectal and Anal Surgery, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou 510641, China
| | - Jin Tan
- The Sixth Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou 510641, China
| | - Weifeng Yang
- Department of Colorectal and Anal Surgery, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou 510641, China
| | - Guanwei Li
- Department of Colorectal and Anal Surgery, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou 510641, China
| | - Xiaoling Pan
- The Sixth Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou 510641, China
| | - Yuying Liu
- The Sixth Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou 510641, China
| | - Feng-Juan Lyu
- The Sixth Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou 510641, China
- Correspondence: (F.-J.L.); (W.L.)
| | - Wanglin Li
- Department of Colorectal and Anal Surgery, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou 510641, China
- Correspondence: (F.-J.L.); (W.L.)
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Bellei B, Migliano E, Picardo M. Therapeutic potential of adipose tissue-derivatives in modern dermatology. Exp Dermatol 2022; 31:1837-1852. [PMID: 35102608 DOI: 10.1111/exd.14532] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Revised: 01/24/2022] [Accepted: 01/28/2022] [Indexed: 12/14/2022]
Abstract
Stem cell-mediated therapies in combination with biomaterial and growth factor-based approaches in regenerative medicine are rapidly evolving with increasing application beyond the dermatologic field. Adipose-derived stem cells (ADSCs) are the more frequently used adult stem cells due to their abundance and easy access. In the case of volumetric defects, adipose tissue can take the shape of defects, restoring the volume and enhancing the regeneration of receiving tissue. When regenerative purposes prevail on volume restoration, the stromal vascular fraction (SVF) rich in staminal cells, purified mesenchymal stem cells (MSCs) or their cell-free derivatives grafting are favoured. The therapeutic efficacy of acellular approaches is explained by the fact that a significant part of the natural propensity of stem cells to repair damaged tissue is ascribable to their secretory activity that combines mitogenic factors, cytokines, chemokines and extracellular matrix components. Therefore, the secretome's ability to modulate multiple targets simultaneously demonstrated preclinical and clinical efficacy in reversing pathological mechanisms of complex conditions such atopic dermatitis (AD), vitiligo, psoriasis, acne and Lichen sclerosus (LS), non-resolving wounds and alopecia. This review analysing both in vivo and in vitro models gives an overview of the clinical relevance of adipose tissue-derivatives such as autologous fat graft, stromal vascular fraction, purified stem cells and secretome for skin disorders application. Finally, we highlighted the major disease-specific limitations and the future perspective in this field.
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Affiliation(s)
- Barbara Bellei
- Laboratory of Cutaneous Physiopathology and Integrated Center of Metabolomics Research, San Gallicano Dermatological Institute, IRCCS, Rome, Italy
| | - Emilia Migliano
- Department of Plastic and Regenerative Surgery, San Gallicano Dermatological Institute, IRCCS, Rome, Italy
| | - Mauro Picardo
- Laboratory of Cutaneous Physiopathology and Integrated Center of Metabolomics Research, San Gallicano Dermatological Institute, IRCCS, Rome, Italy
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Vargel İ, Tuncel A, Baysal N, Hartuç-Çevik İ, Korkusuz F. Autologous Adipose-Derived Tissue Stromal Vascular Fraction (AD-tSVF) for Knee Osteoarthritis. Int J Mol Sci 2022; 23:13517. [PMID: 36362308 PMCID: PMC9658499 DOI: 10.3390/ijms232113517] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2022] [Revised: 10/28/2022] [Accepted: 10/30/2022] [Indexed: 07/30/2023] Open
Abstract
Adipose tissue contains adult mesenchymal stem cells that may modulate the metabolism when applied to other tissues. Stromal vascular fraction (SVF) can be isolated from adipose tissue mechanically and/or enzymatically. SVF was recently used to decrease the pain and improve the function of knee osteoarthritis (OA) patients. Primary and/or secondary OA causes inflammation and degeneration in joints, and regenerative approaches that may modify the natural course of the disease are limited. SVF may modulate inflammation and initiate regeneration in joint tissues by initiating a paracrine effect. Chemokines released from SVF may slow down degeneration and stimulate regeneration in joints. In this review, we overviewed articular joint cartilage structures and functions, OA, and macro-, micro-, and nano-fat isolation techniques. Mechanic and enzymatic SVF processing techniques were summarized. Clinical outcomes of adipose tissue derived tissue SVF (AD-tSVF) were evaluated. Medical devices that can mechanically isolate AD-tSVF were listed, and publications referring to such devices were summarized. Recent review manuscripts were also systematically evaluated and included. Transferring adipose tissues and cells has its roots in plastic, reconstructive, and aesthetic surgery. Micro- and nano-fat is also transferred to other organs and tissues to stimulate regeneration as it contains regenerative cells. Minimal manipulation of the adipose tissue is recently preferred to isolate the regenerative cells without disrupting them from their natural environment. The number of patients in the follow-up studies are recently increasing. The duration of follow up is also increasing with favorable outcomes from the short- to mid-term. There are however variations for mean age and the severity of knee OA patients between studies. Positive outcomes are related to the higher number of cells in the AD-tSVF. Repetition of injections and concomitant treatments such as combining the AD-tSVF with platelet rich plasma or hyaluronan are not solidified. Good results were obtained when combined with arthroscopic debridement and micro- or nano-fracture techniques for small-sized cartilage defects. The optimum pressure applied to the tissues and cells during filtration and purification of the AD-tSVF is not specified yet. Quantitative monitoring of articular joint cartilage regeneration by ultrasound, MR, and synovial fluid analysis as well as with second-look arthroscopy could improve our current knowledge on AD-tSVF treatment in knee OA. AD-tSVF isolation techniques and technologies have the potential to improve knee OA treatment. The duration of centrifugation, filtration, washing, and purification should however be standardized. Using gravity-only for isolation and filtration could be a reasonable approach to avoid possible complications of other methodologies.
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Affiliation(s)
- İbrahim Vargel
- Department of Plastic Reconstructive and Aesthetic Surgery, Medical Faculty, Hacettepe University, Altındag, Ankara 06230, Turkey
| | - Ali Tuncel
- Department of Chemical Engineering, Engineering Faculty, Hacettepe University, Universiteler Mahallesi, Hacettepe Beytepe Campus #31, Çankaya, Ankara 06800, Turkey
| | - Nilsu Baysal
- Medical Faculty, Hacettepe University, Altındag, Ankara 06230, Turkey
| | - İrem Hartuç-Çevik
- Department of Sports Medicine, Medical Faculty, Hacettepe University, Altındag, Ankara 06230, Turkey
| | - Feza Korkusuz
- Department of Sports Medicine, Medical Faculty, Hacettepe University, Altındag, Ankara 06230, Turkey
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Liu P, Gurung B, Afzal I, Santin M, Sochart DH, Field RE, Kader DF, Asopa V. The composition of cell-based therapies obtained from point-of-care devices/systems which mechanically dissociate lipoaspirate: a scoping review of the literature. J Exp Orthop 2022; 9:103. [PMID: 36209438 PMCID: PMC9548462 DOI: 10.1186/s40634-022-00537-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Accepted: 09/15/2022] [Indexed: 11/15/2022] Open
Abstract
PURPOSE Cell-based therapies using lipoaspirate are gaining popularity in orthopaedics due to their hypothesised regenerative potential. Several 'point-of-care' lipoaspirate-processing devices/systems have become available to isolate cells for therapeutic use, with published evidence reporting their clinical relevance. However, few studies have analysed the composition of their 'minimally-manipulated' cellular products in parallel, information that is vital to understand the mechanisms by which these therapies may be efficacious. This scoping review aimed to identify devices/systems using mechanical-only processing of lipoaspirate, the constituents of their cell-based therapies and where available, clinical outcomes. METHODS PRISMA extension for scoping reviews guidelines were followed. MEDLINE, Embase and PubMed databases were systematically searched to identify relevant articles until 21st April 2022. Information relating to cellular composition and clinical outcomes for devices/systems was extracted. Further information was also obtained by individually searching the devices/systems in the PubMed database, Google search engine and contacting manufacturers. RESULTS 2895 studies were screened and a total of 15 articles (11 = Level 5 evidence) fulfilled the inclusion criteria. 13 unique devices/systems were identified from included studies. All the studies reported cell concentration (cell number regardless of phenotype per millilitre of lipoaspirate) for their devices/systems (range 0.005-21 × 106). Ten reported cell viability (the measure of live cells- range 60-98%), 11 performed immuno-phenotypic analysis of the cell-subtypes and four investigated clinical outcomes of their cellular products. Only two studies reported all four of these parameters. CONCLUSION When focussing on cell concentration, cell viability and MSC immuno-phenotypic analysis alone, the most effective manual devices/systems were ones using filtration and cutting/mincing. However, it was unclear whether high performance in these categories would translate to improved clinical outcomes. Due to the lack of standardisation and heterogeneity of the data, it was also not possible to draw any reliable conclusions and determine the role of these devices/systems in clinical practice at present. LEVEL OF EVIDENCE Level V Therapeutic.
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Affiliation(s)
- Perry Liu
- South West London Elective Orthopaedic Centre, Epsom, UK.
| | - Binay Gurung
- South West London Elective Orthopaedic Centre, Epsom, UK
| | - Irrum Afzal
- South West London Elective Orthopaedic Centre, Epsom, UK
| | - Matteo Santin
- Centre for Regenerative Medicine and Devices, School of Applied Sciences, University of Brighton, Brighton, UK
| | | | - Richard E Field
- South West London Elective Orthopaedic Centre, Epsom, UK
- University of London, St George's, London, UK
| | - Deiary F Kader
- South West London Elective Orthopaedic Centre, Epsom, UK
| | - Vipin Asopa
- South West London Elective Orthopaedic Centre, Epsom, UK
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Micro-fragmented adipose tissue cellular composition varies by processing device and analytical method. Sci Rep 2022; 12:16107. [PMID: 36167761 PMCID: PMC9515206 DOI: 10.1038/s41598-022-20581-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2022] [Accepted: 09/15/2022] [Indexed: 11/10/2022] Open
Abstract
Autologous adipose-derived biologics are of clinical interest based on accessibility of adipose tissue, a rich source of progenitor and immunomodulatory cells. Micro-fragmented adipose tissue (MFAT) preserves the cellular niche within intact extracellular matrix, potentially offering benefit over enzymatically-liberated stromal vascular fraction (SVF), however lack of standardized analyses complicate direct comparison of these products. In this study, MFAT from LipoGems® and AutoPose™ Restore systems, which utilize different washing and resizing methods, was analyzed for cellular content using different techniques. Flow cytometry was performed on SVF, with or without culture, and on the adherent cell population that naturally migrated from undigested MFAT. Cytokine release during culture was also assessed. SVF contained more diverse progenitor populations, while MFAT outgrowth contained lower cell concentrations of predominantly mesenchymal stromal cells (MSC). MSCs were significantly higher in MFAT from the AutoPose System for all analyses, with increased cytokine secretion characterized by high levels of anti-inflammatory and low to non-detectable inflammatory cytokines. These results demonstrate that cellularity depends on MFAT processing methods, and different techniques can be employed to evaluate graft cellularity. Comparisons of cell concentrations determined via these methods could be used to better interpret inter-study variability.
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Regulation of Adipose Progenitor Cell Expansion in a Novel Micro-Physiological Model of Human Adipose Tissue Mimicking Fibrotic and Pro-Inflammatory Microenvironments. Cells 2022; 11:cells11182798. [PMID: 36139371 PMCID: PMC9496930 DOI: 10.3390/cells11182798] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2022] [Revised: 08/31/2022] [Accepted: 09/05/2022] [Indexed: 11/17/2022] Open
Abstract
The expansion of adipose progenitor cells (APCs) plays an important role in the regeneration of the adipose tissue in physiological and pathological situations. The major role of CD26-expressing APCs in the generation of adipocytes has recently been highlighted, revealing that the CD26 APC subtype displays features of multipotent stem cells, giving rise to CD54- and CD142-expressing preadipocytes. However, a relevant human in vitro model to explore the regulation of the APC subpopulation expansion in lean and obese adipose tissue microenvironments is still lacking. In this work, we describe a novel adipose tissue model, named ExAdEx, that can be obtained from cosmetic surgery wastes. ExAdEx products are adipose tissue units maintaining the characteristics and organization of adipose tissue as it presents in vivo. The model was viable and metabolically active for up to two months and could adopt a pathological-like phenotype. The results revealed that inflammatory and fibrotic microenvironments differentially regulated the expansion of the CD26 APC subpopulation and its CD54 and CD142 APC progenies. The approach used significantly improves the method of generating adipose tissue models, and ExAdEx constitutes a relevant model that could be used to identify pathways promoting the expansion of APCs in physiological and pathological microenvironments.
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Adipose stromal vascular fraction: a promising treatment for severe burn injury. Hum Cell 2022; 35:1323-1337. [PMID: 35906507 DOI: 10.1007/s13577-022-00743-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2022] [Accepted: 06/24/2022] [Indexed: 11/04/2022]
Abstract
Thermal skin burn injury affects both adults and children globally. Severe burn injury affects a patient's life psychologically, cosmetically, and socially. The pathophysiology of burn injury is well known. Due to the complexity of burn pathophysiology, the development of specific treatment aiding in tissue regeneration is required. Treatment of burn injury depends on burn severity, size of the burn and availability of donor site. Burn healing requires biochemical and cellular events to ensure better cell response to biochemical signals of the healing process. This led to the consideration of using cell therapy for severe burn injury. Adult mesenchymal stem cells have become a therapeutic option because of their ability for self-renewal and differentiation. Adipose stromal vascular fraction (SVF), isolated from adipose tissues, is a heterogeneous cell population that contains adipose-derived stromal/stem cells (ADSC), stromal, endothelial, hematopoietic and pericytic lineages. SVF isolation has advantages over other types of cells; such as heterogeneity of cells, lower invasive extraction procedure, high yield of cells, and fast and easy isolation. Therefore, SVF has many characteristics that enable them to be a therapeutic option for burn treatment. Studies have been conducted mostly in animal models to investigate their therapeutic potential for burn injury. They can be used alone or in combination with other treatment options. Treatment with both ADSCs and/or SVF enhances burn healing through increasing re-epithelization, angiogenesis and decreasing inflammation and scar formation. Research needs to be conducted for a better understanding of the SVF mechanism in burn healing and to optimize current techniques for enhanced treatment outcomes.
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Ivanovska A, Wang M, Arshaghi TE, Shaw G, Alves J, Byrne A, Butterworth S, Chandler R, Cuddy L, Dunne J, Guerin S, Harry R, McAlindan A, Mullins RA, Barry F. Manufacturing Mesenchymal Stromal Cells for the Treatment of Osteoarthritis in Canine Patients: Challenges and Recommendations. Front Vet Sci 2022; 9:897150. [PMID: 35754551 PMCID: PMC9230578 DOI: 10.3389/fvets.2022.897150] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2022] [Accepted: 04/14/2022] [Indexed: 12/28/2022] Open
Abstract
The recent interest in advanced biologic therapies in veterinary medicine has opened up opportunities for new treatment modalities with considerable clinical potential. Studies with mesenchymal stromal cells (MSCs) from animal species have focused on in vitro characterization (mostly following protocols developed for human application), experimental testing in controlled studies and clinical use in veterinary patients. The ability of MSCs to interact with the inflammatory environment through immunomodulatory and paracrine mechanisms makes them a good candidate for treatment of inflammatory musculoskeletal conditions in canine species. Analysis of existing data shows promising results in the treatment of canine hip dysplasia, osteoarthritis and rupture of the cranial cruciate ligament in both sport and companion animals. Despite the absence of clear regulatory frameworks for veterinary advanced therapy medicinal products, there has been an increase in the number of commercial cell-based products that are available for clinical applications, and currently the commercial use of veterinary MSC products has outpaced basic research on characterization of the cell product. In the absence of quality standards for MSCs for use in canine patients, their safety, clinical efficacy and production standards are uncertain, leading to a risk of poor product consistency. To deliver high-quality MSC products for veterinary use in the future, there are critical issues that need to be addressed. By translating standards and strategies applied in human MSC manufacturing to products for veterinary use, in a collaborative effort between stem cell scientists and veterinary researchers and surgeons, we hope to facilitate the development of quality standards. We point out critical issues that need to be addressed, including a much higher level of attention to cell characterization, manufacturing standards and release criteria. We provide a set of recommendations that will contribute to the standardization of cell manufacturing methods and better quality assurance.
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Affiliation(s)
- Ana Ivanovska
- Regenerative Medicine Institute (REMEDI), Biosciences, National University of Ireland Galway, Galway, Ireland
| | - Mengyu Wang
- Regenerative Medicine Institute (REMEDI), Biosciences, National University of Ireland Galway, Galway, Ireland
| | - Tarlan Eslami Arshaghi
- Regenerative Medicine Institute (REMEDI), Biosciences, National University of Ireland Galway, Galway, Ireland
| | - Georgina Shaw
- Regenerative Medicine Institute (REMEDI), Biosciences, National University of Ireland Galway, Galway, Ireland
| | | | | | | | - Russell Chandler
- Orthopaedic Referral Service, Alphavet Veterinary Centre, Newport, United Kingdom
| | - Laura Cuddy
- Small Animal Surgery, Canine Sports Medicine and Rehabilitation, Veterinary Specialists Ireland, Summerhill, Ireland
| | - James Dunne
- Knocknacarra Veterinary Clinic, Ark Vets Galway, Galway, Ireland
| | - Shane Guerin
- Small Animal Surgery, Gilabbey Veterinary Hospital, Cork, Ireland
| | | | - Aidan McAlindan
- Northern Ireland Veterinary Specialists, Hillsborough, United Kingdom
| | - Ronan A Mullins
- Department of Small Animal Surgery, School of Veterinary Medicine, University College Dublin, Dublin, Ireland
| | - Frank Barry
- Regenerative Medicine Institute (REMEDI), Biosciences, National University of Ireland Galway, Galway, Ireland
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Hung MJ, Tsai CP, Ying TH, Chen GD, Su HL, Tseng CJ. Improved symptoms and signs of refractory interstitial cystitis in women after intravesical Nanofat plus platelet-rich plasma grafting: A pilot study. J Chin Med Assoc 2022; 85:730-735. [PMID: 35507021 DOI: 10.1097/jcma.0000000000000735] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
Interstitial cystitis/bladder pain syndrome (IC/BPS) is characterized by bladder pain accompanied by irritative urinary symptoms, and typical cystoscopic and histological features. In this pilot study, we assessed the impact of lesion-targeted bladder injection therapy using a biocellular regenerative medicine on patients with refractory IC/BPS. The medicine, which was an autologous emulsified fat (Nanofat) and platelet-rich plasma (PRP) combination, was prepared intraoperatively. Six patients (aged 40-54 years), who completed a standard protocol of four consecutive treatments at 3-month intervals, were followed up at 6 months postoperatively. All patients (100%) reported marked (+3; +3 ~ -3) improvement of their overall bladder conditions. Mean bladder pain (from 8.2 to 1.7; range: 0 ~ 10), IC-related symptoms (from 18.5 to 5.7; range: 0 ~ 20), and bother (from 14.8 to 3.8; range: 0 ~ 16) improved significantly (p < 0.01). The normalization of bladder mucosal morphology with treatments was remarkable under cystoscopic examination, and no significant adverse events were found. The cultured mesenchymal stem cells from Nanofat samples of the six patients were verified in vitro. Our preliminary results suggest novel intravesical therapy with autologous Nanofat plus PRP grafting is safe and effective for refractory IC/BPS. Surgical efficacy might be attributed to an in vivo tissue engineering process.
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Affiliation(s)
- Man-Jung Hung
- Department of Obstetrics and Gynecology, Chung Shan Medical University Hospital, Taichung, Taiwan, ROC
- Department of Obstetrics and Gynecology, School of Medicine, Colleague of Medicine, Chung Shan Medical University, Taichung, Taiwan, ROC
| | - Ching-Pei Tsai
- Department of Obstetrics and Gynecology, Taichung Veterans General Hospital, Taichung, Taiwan, ROC
| | - Tsung-Ho Ying
- Department of Obstetrics and Gynecology, Chung Shan Medical University Hospital, Taichung, Taiwan, ROC
- Department of Obstetrics and Gynecology, School of Medicine, Colleague of Medicine, Chung Shan Medical University, Taichung, Taiwan, ROC
| | - Gin-Den Chen
- Department of Obstetrics and Gynecology, Chung Shan Medical University Hospital, Taichung, Taiwan, ROC
- Department of Obstetrics and Gynecology, School of Medicine, Colleague of Medicine, Chung Shan Medical University, Taichung, Taiwan, ROC
| | - Hong-Lin Su
- Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan, ROC
| | - Chih-Jen Tseng
- Department of Obstetrics and Gynecology, Chung Shan Medical University Hospital, Taichung, Taiwan, ROC
- Department of Obstetrics and Gynecology, School of Medicine, Colleague of Medicine, Chung Shan Medical University, Taichung, Taiwan, ROC
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Montanari M, Burattini S, Ciacci C, Ambrogini P, Carloni S, Balduini W, Lopez D, Panza G, Papa S, Canonico B. Automated–Mechanical Procedure Compared to Gentle Enzymatic Tissue Dissociation in Cell Function Studies. Biomolecules 2022; 12:biom12050701. [PMID: 35625628 PMCID: PMC9138555 DOI: 10.3390/biom12050701] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Revised: 05/11/2022] [Accepted: 05/12/2022] [Indexed: 02/04/2023] Open
Abstract
The first step to obtain a cellular suspension from tissues is the disaggregation procedure. The cell suspension method has to provide a representative sample of the different cellular subpopulations and to maximize the number of viable functional cells. Here, we analyzed specific cell functions in cell suspensions from several rat tissues obtained by two different methods, automated–mechanical and enzymatic disaggregation. Flow cytometric, confocal, and ultrastructural (TEM) analyses were applied to the spleen, testis, liver and other tissues. Samples were treated by an enzymatic trypsin solution or processed by the Medimachine II (MMII). The automated–mechanical and enzymatic disaggregation procedures have shown to work similarly in some tissues, which displayed comparable amounts of apoptotic/necrotic cells. However, cells obtained by the enzyme-free Medimachine II protocols show a better preservation lysosome and mitochondria labeling, whereas the enzymatic gentle dissociation appears to constantly induce a lower amount of intracellular ROS; nevertheless, lightly increased ROS can be recognized as a complimentary signal to promote cell survival. Therefore, MMII represents a simple, fast, and standardized method for tissue processing, which allows to minimize bias arising from the operator’s ability. Our study points out technical issues to be adopted for specific organs and tissues to obtain functional cells.
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Affiliation(s)
- Mariele Montanari
- Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, Italy; (M.M.); (S.B.); (C.C.); (P.A.); (S.C.); (W.B.); (D.L.); (G.P.); (S.P.)
| | - Sabrina Burattini
- Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, Italy; (M.M.); (S.B.); (C.C.); (P.A.); (S.C.); (W.B.); (D.L.); (G.P.); (S.P.)
| | - Caterina Ciacci
- Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, Italy; (M.M.); (S.B.); (C.C.); (P.A.); (S.C.); (W.B.); (D.L.); (G.P.); (S.P.)
| | - Patrizia Ambrogini
- Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, Italy; (M.M.); (S.B.); (C.C.); (P.A.); (S.C.); (W.B.); (D.L.); (G.P.); (S.P.)
| | - Silvia Carloni
- Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, Italy; (M.M.); (S.B.); (C.C.); (P.A.); (S.C.); (W.B.); (D.L.); (G.P.); (S.P.)
| | - Walter Balduini
- Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, Italy; (M.M.); (S.B.); (C.C.); (P.A.); (S.C.); (W.B.); (D.L.); (G.P.); (S.P.)
| | - Daniele Lopez
- Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, Italy; (M.M.); (S.B.); (C.C.); (P.A.); (S.C.); (W.B.); (D.L.); (G.P.); (S.P.)
- Department of Pure and Applied Sciences (DiSPeA), University of Urbino Carlo Bo, 61029 Urbino, Italy
| | - Giovanna Panza
- Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, Italy; (M.M.); (S.B.); (C.C.); (P.A.); (S.C.); (W.B.); (D.L.); (G.P.); (S.P.)
| | - Stefano Papa
- Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, Italy; (M.M.); (S.B.); (C.C.); (P.A.); (S.C.); (W.B.); (D.L.); (G.P.); (S.P.)
| | - Barbara Canonico
- Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, Italy; (M.M.); (S.B.); (C.C.); (P.A.); (S.C.); (W.B.); (D.L.); (G.P.); (S.P.)
- Correspondence:
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Lau CS, Chua J, Pena EM, Lim J, Saigo L, Goh BT. A Porcine Model Using Adipose Stem Cell-Loaded Scaffolds for Alveolar Ridge Augmentation. Tissue Eng Part C Methods 2022; 28:228-237. [PMID: 35442100 DOI: 10.1089/ten.tec.2022.0062] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Tooth loss greatly affects a person's quality of life and many turn to dental implants to replace lost teeth. The success of a dental implant depends on the amount of alveolar bone supporting the implant, and thus, bone augmentation is often necessary to preserve or build up bone volume in the alveolar ridge. Bone can be augmented with autogenous bone, allografts, or xenografts, but the limitations of such natural bone grafts prompt researchers to develop synthetic scaffolds supplemented with cells and/or bioactive agents as alternative bone grafts. The translation of these combination scaffolds from the laboratory to the clinic requires reliable experimental models that can simulate the clinical conditions in human patients. In this article, we describe the use of a porcine alveolar defect model as a platform to evaluate the efficacy of a novel combination of a three-dimensional-printed polycaprolactone-tricalcium phosphate (PCL-TCP) scaffold and adipose-derived mesenchymal stem cells (AD-MSCs) in lateral alveolar augmentation. The surgical protocol for the defect creation and regenerative surgery, as well as analytical methods to determine the extent of tissue regeneration, are described and discussed.
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Affiliation(s)
- Chau Sang Lau
- Oral Health Academic Clinical Programme, Duke-NUS Medical School, Singapore, Singapore.,National Dental Research Institute Singapore, National Dental Centre Singapore, Singapore, Singapore
| | - Jasper Chua
- National Heart Research Institute Singapore, National Heart Centre Singapore, Singapore, Singapore.,Cardiovascular and Metabolic Disorder Programme, Duke-NUS Medical School, Singapore, Singapore
| | - Edgar Macabe Pena
- SingHealth Experimental Medicine Centre and National Large Animal Research Facility, Singapore Health Services Pte Ltd., Singapore, Singapore
| | - Jing Lim
- Osteopore International Pte Ltd., Singapore, Singapore
| | - Leonardo Saigo
- Department of Oral and Maxillofacial Surgery, National Dental Centre Singapore, Singapore, Singapore
| | - Bee Tin Goh
- Oral Health Academic Clinical Programme, Duke-NUS Medical School, Singapore, Singapore.,National Dental Research Institute Singapore, National Dental Centre Singapore, Singapore, Singapore.,Department of Oral and Maxillofacial Surgery, National Dental Centre Singapore, Singapore, Singapore
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Jia Z, Kang B, Cai Y, Chen C, Yu Z, Li W, Zhang W. Cell-free fat extract attenuates osteoarthritis via chondrocytes regeneration and macrophages immunomodulation. Stem Cell Res Ther 2022; 13:133. [PMID: 35365233 PMCID: PMC8973552 DOI: 10.1186/s13287-022-02813-3] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2022] [Accepted: 03/02/2022] [Indexed: 01/15/2023] Open
Abstract
Background The prevalence of osteoarthritis (OA) is increasing, yet clinically effective and economical treatments are unavailable. We have previously proposed a cell-free fat extract (CEFFE) containing multiple cytokines, which possessed antiapoptotic, anti-oxidative, and proliferation promotion functions, as a “cell-free” strategy. In this study, we aimed to evaluate the therapeutic effect of CEFFE in vivo and in vitro. Methods In vivo study, sodium iodoacetate-induced OA rats were treated with CEFFE by intra-articular injections for 8 weeks. Behavioral experiments were performed every two weeks. Histological analyses, anti-type II collagen, and toluidine staining provided structural evaluation. Macrophage infiltration was assessed by anti-CD68 and anti-CD206 staining. In vitro study, the effect of CEFFE on macrophage polarization and secretory factors was evaluated by flow cytometry, immunofluorescence, and quantitative reverse-transcription polymerase chain reaction (qRT-PCR). The effect of CEFFE on cartilage regeneration was accessed by cell counting kit-8 assay and qRT-PCR. The generation of reactive oxygen species (ROS) and levels of ROS-related enzymes were investigated by qRT-PCR and western blotting. Results In rat models with sodium iodoacetate (MIA)-induced OA, CEFFE increased claw retraction pressure while decreasing bipedal pressure in a dose-dependent manner. Moreover, CEFFE promoted cartilage structure restoration and increased the proportion of CD206+ macrophages in the synovium. In vitro, CEFFE decreased the proportion of CD86+ cells and reduced the expression of pro-inflammatory factors in LPS + IFN-γ induced Raw 264.7. In addition, CEFFE decreased the expression of interleukin-6 and ADAMTs-5 and promoted the expression of SOX-9 in mouse primary chondrocytes. Besides, CEFFE reduced the intracellular levels of reactive oxygen species in both in vitro models through regulating ROS-related enzymes. Conclusions CEFFE inhibits the progression of OA by promoting cartilage regeneration and limiting low-grade joint inflammation. Graphical abstract ![]()
Supplementary Information The online version contains supplementary material available at 10.1186/s13287-022-02813-3.
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Affiliation(s)
- Zhuoxuan Jia
- Department of Plastic and Reconstructive Surgery, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Tissue Engineering, National Tissue Engineering Center of China, 639 ZhiZaoJu Road, Shanghai, 200011, China
| | - Bijun Kang
- Department of Plastic and Reconstructive Surgery, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Tissue Engineering, National Tissue Engineering Center of China, 639 ZhiZaoJu Road, Shanghai, 200011, China
| | - Yizuo Cai
- Department of Plastic and Reconstructive Surgery, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Tissue Engineering, National Tissue Engineering Center of China, 639 ZhiZaoJu Road, Shanghai, 200011, China
| | - Chingyu Chen
- Department of Plastic and Reconstructive Surgery, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Tissue Engineering, National Tissue Engineering Center of China, 639 ZhiZaoJu Road, Shanghai, 200011, China
| | - Zheyuan Yu
- Department of Plastic and Reconstructive Surgery, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Tissue Engineering, National Tissue Engineering Center of China, 639 ZhiZaoJu Road, Shanghai, 200011, China.
| | - Wei Li
- Department of Plastic and Reconstructive Surgery, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Tissue Engineering, National Tissue Engineering Center of China, 639 ZhiZaoJu Road, Shanghai, 200011, China.
| | - Wenjie Zhang
- Department of Plastic and Reconstructive Surgery, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Tissue Engineering, National Tissue Engineering Center of China, 639 ZhiZaoJu Road, Shanghai, 200011, China.
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Hendawy H, Kaneda M, Yoshida T, Metwally E, Hambe L, Yoshida T, Shimada K, Tanaka R. Heterogeneity of Adipose Stromal Vascular Fraction Cells from the Different Harvesting Sites in Rats. Anat Rec (Hoboken) 2022; 305:3410-3421. [PMID: 35332993 DOI: 10.1002/ar.24915] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2022] [Revised: 03/04/2022] [Accepted: 03/08/2022] [Indexed: 11/09/2022]
Abstract
In both veterinary and human health, regenerative medicine offers a promising cure for various disorders. One of the rate-limiting challenges in regenerative medicine is the considerable time and technique required to expand and grow cells in culture. Therefore, the stromal vascular fraction (SVF) shows a significant promise for various cell therapy approaches. The present study aimed to define and investigate the optimal harvest site of freshly isolated SVF cells from various adipose tissue (AT) depot sites in the female Sprague-Dawley (S.D.) rat. First, Hematoxylin and eosin (H&E) were used to analyze the morphological variations in AT samples from peri-ovarian, peri-renal, mesenteric, and omental sites. The presence of putative stromal cells positive CD34 was detected using immunohistochemistry. Then, the isolated SVF cells were examined for cell viability and cellular yield differences. Finally, the expression of mesenchymal stem cells and hematopoietic markers in the SVF cells subpopulation was studied using flow cytometry. The pluripotent gene expression profile was also evaluated. CD34 staining of the omental AT was substantially higher than those of other anatomical sites. Despite having the least quantity of fat, omental AT has the highest SVF cell fraction and viable cells. Along with CD90 and CD44 higher expression, Oct4, Sox2, and Rex-1 genes levels were higher in SVF cells isolated from the omental AT. To conclude, omental fat is the best candidate for SVF cell isolation in female S.D. rats with the highest SVF cell fraction with higher MSCs phenotypes and pluripotency gene expression.
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Affiliation(s)
- Hanan Hendawy
- Laboratory of Veterinary Surgery, Tokyo University of Agriculture and Technology, Tokyo183-8509, Japan.,Department of Veterinary Surgery, Faculty of Veterinary Medicine, Suez Canal University, Egypt
| | - Masahiro Kaneda
- Laboratory of Veterinary Anatomy, Division of Animal Life Science, Tokyo University of Agriculture and Technology, Tokyo, Japan
| | - Tadashi Yoshida
- Department of Applied Biological Science, Tokyo University of Agriculture and Technology, Tokyo 183-8509, Japan
| | - Elsayed Metwally
- Department of cytology and Histology, Faculty of Veterinary Medicine, Suez Canal University, Egypt
| | - Lina Hambe
- Laboratory of Veterinary Surgery, Tokyo University of Agriculture and Technology, Tokyo183-8509, Japan
| | - Tomohiko Yoshida
- Laboratory of Veterinary Surgery, Tokyo University of Agriculture and Technology, Tokyo183-8509, Japan
| | - Kazumi Shimada
- Laboratory of Veterinary Surgery, Tokyo University of Agriculture and Technology, Tokyo183-8509, Japan
| | - Ryou Tanaka
- Laboratory of Veterinary Surgery, Tokyo University of Agriculture and Technology, Tokyo183-8509, Japan
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In Vivo Evaluation of Mechanically Processed Stromal Vascular Fraction in a Chamber Vascularized by an Arteriovenous Shunt. Pharmaceutics 2022; 14:pharmaceutics14020417. [PMID: 35214149 PMCID: PMC8880586 DOI: 10.3390/pharmaceutics14020417] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Revised: 02/01/2022] [Accepted: 02/07/2022] [Indexed: 11/16/2022] Open
Abstract
Mechanically processed stromal vascular fraction (mSVF) is a promising source for regenerative purposes. To study the in vivo fate of the mSVF, we herein used a vascularized tissue engineering chamber that insulates the target mSVF from the surrounding environment. In contrast to previous models, we propose an arteriovenous (AV) shunt between saphenous vessels in rats without a venous graft. Mechanical SVF was processed from the fat pads of male Sprague Dawley rats, mixed with a fibrin hydrogel and implanted into an inguinal tissue engineering chamber. An arteriovenous shunt was established between saphenous artery and vein. On the contralateral side, an mSVF-fibrin hydrogel mix without vascular axis served as a non-vascularized control. After two and six weeks, rats were sacrificed for further analysis. Mechanical SVF showed significant numbers of mesenchymal stromal cells. Vascularized mSVF explants gained weight over time. Perilipin and CD31 expression were significantly higher in the mSVF explants after six weeks while no difference in DAPI positive cells, collagen deposition and FABP4 expression was observed. Morphologically, no differentiated adipocytes but a dense cell-rich tissue with perilipin-positive cells was found after six weeks. The phosphorylation of ERK1/2 was significantly enhanced after six weeks while Akt activation remained unaltered. Finally, mSVF explants stably expressed and released VEGF, bFGF and TGFb. Vascularized mSVF is able to proliferate and express adipocyte-specific markers. The AV shunt model is a valuable refinement of currently existing AV loop models in the rat which contributes to the fundamental 3R principles of animal research.
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Weinzierl A, Harder Y, Schmauss D, Menger MD, Laschke MW. Boosting Tissue Vascularization: Nanofat as a Potential Source of Functional Microvessel Segments. Front Bioeng Biotechnol 2022; 10:820835. [PMID: 35186904 PMCID: PMC8854281 DOI: 10.3389/fbioe.2022.820835] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2021] [Accepted: 01/14/2022] [Indexed: 11/13/2022] Open
Abstract
Nanofat is increasingly applied in plastic surgery for the improvement of scar quality and skin rejuvenation. However, little is known about the underlying regenerative mechanisms. Therefore, we herein investigated nanofat grafts in a murine dorsal skinfold chamber model. Nanofat generated from subcutaneous, inguinal adipose tissue of green fluorescent protein (GFP)+ C57BL/6 male and female donor mice was injected intracutaneously into dorsal skinfold chambers of gender-matched GFP− wild-type mice. The vascularization and tissue composition of the grafted nanofat were analyzed by means of intravital fluorescence microscopy, histology and immunohistochemistry over an observation period of 14 days. The freshly generated nanofat consisted of small fragments of perilipin+ adipocytes surrounded by Sirius red+ collagen fibers and still contained intact CD31+/GFP+ vessel segments. After transplantation into the dorsal skinfold chamber, these vessel segments survived and developed interconnections to the surrounding CD31+/GFP− host microvasculature. Accordingly, the grafted nanofat rapidly vascularized and formed new microvascular networks with a high functional microvessel density on day 14 without marked differences between male and female mice. Even though further research is needed to confirm these findings, the present study suggests that nanofat boosts tissue vascularization. Thus, nanofat may represent a versatile resource for many applications in tissue engineering and regenerative medicine.
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Affiliation(s)
- Andrea Weinzierl
- Institute for Clinical & Experimental Surgery, Saarland University, Homburg, Germany
- *Correspondence: Andrea Weinzierl,
| | - Yves Harder
- Department of Plastic, Reconstructive and Aesthetic Surgery, Ospedale Regionale di Lugano, Ente Ospedaliero Cantonale (EOC), Lugano, Switzerland
- Faculty of Biomedical Sciences, Università Della Svizzera Italiana, Lugano, Switzerland
| | - Daniel Schmauss
- Department of Plastic, Reconstructive and Aesthetic Surgery, Ospedale Regionale di Lugano, Ente Ospedaliero Cantonale (EOC), Lugano, Switzerland
- Faculty of Biomedical Sciences, Università Della Svizzera Italiana, Lugano, Switzerland
| | - Michael D. Menger
- Institute for Clinical & Experimental Surgery, Saarland University, Homburg, Germany
| | - Matthias W. Laschke
- Institute for Clinical & Experimental Surgery, Saarland University, Homburg, Germany
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Copcu HE. Indication-based protocols with different solutions for mechanical stromal-cell transfer. Scars Burn Heal 2022; 8:20595131211047830. [PMID: 35003762 PMCID: PMC8738882 DOI: 10.1177/20595131211047830] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
Background Regenerative medicine is the fastest developing branch of plastic surgery in recent times. Adipose tissue is one of the largest and most important sources in the body for stromal cells. Although mechanical isolation methods are both very popular and have many advantages, they still have no accepted protocols. Objective We developed new protocols called indication-based protocols (IPs) for standardization and new techniques called mechanical stromal-cell transfer (MEST) by using ultra-sharp blades and dilution of adipose tissue with different solutions (saline, Ringer and 5% Dextrose) Methods & material: In order to obtain the desired physical structure (liquid, gel, solid) and the desired volume, four different types of IPs have been defined. Adipose tissue was prediluted with different solutions using 10 or 20 cc injectors in IPs 1 and 2, while condensed adipose tissue was used directly in IPs 3 and 4. Results In MEST, stromal cells were obtained from 100 mL of condensed fat using different IPs with 92% mean viability and cell counts of 26.80–91.90 × 106. Stromal cells can be obtained in the desired form and number of cells by using four different IPs. Conclusion Isolation of stromal cells by cutting fat with sharp blades will prevent the death of fat tissue and stromal cells and will allow high viability and cell count with our new technique. Predilution with different solutions: Diluting the condensed adipose tissue with the desired solutions (saline, Ringer or 5% Dextrose) before the adinizing process will provide even more stromal cells. Lay Summary Obtaining regenerative stromal cells from adipose tissue can be done by two methods: Enzymatic and mechanical. Mechanical methods have many advantages. Although mechanical stromal cell extraction from adipose tissue is very popular and many techniques have been described, there are still no accepted protocols, definition for the end product, and no consensus on the status of the stromal cells. In this study, stromal cells were obtained mechanically by using ultra-sharp blade systems, without exposing adipose tissue to blunt trauma. Thus, a higher number of cells and higher viability could be obtained. An “Indication based” protocol has been defined for the first time in order to obtain the desired number and status (solid, semi-solid, liquid) end product. Diluting the condensed adipose tissue with the desired solutions (saline, Ringer or 5% Dextrose) before the adinizing process will provide even more stromal cells. This will provide an opportunity for clinicians to obtain and apply a stromal cell solution for different indications in different anatomical regions.
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Affiliation(s)
- H Eray Copcu
- Aesthetic, Plastic and Reconstructive Surgery, G-CAT (Gene, Cell and Tissue) Academy, StemRegen Department, Gebze, Kocaeli, Turkey
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Jha NK, Kamal MA, Kesari KK, Jha SK, Jeyaraman M, Muthu S, Jain R, Satish AS, Garg N, Mishra PC, Swati K, Parkash A, Ojha S, Roychoudhury S, Kumar D, Ruokolainen J. Total Stromal Fraction (TSF) - Fortified Adipose Tissue-Derived Stem
Cells Source: An Emerging Regenerative Realm Against COVID-19 Induced
Pulmonary Compromise. CORONAVIRUSES 2022; 3. [DOI: 10.2174/2666796702666210908151708] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/03/2021] [Revised: 05/24/2021] [Accepted: 06/17/2021] [Indexed: 02/08/2023]
Abstract
:
The inception of the COVID-19 pandemic has jeopardized humanity with markedly dampening
of worldwide resources. The viral infection may present with varying signs and symptoms,
imitating pneumonia and seasonal flu. With a gradual course, this may progress and result in the
deadliest state of acute respiratory distress syndrome (ARDS) and acute lung injury (ALI). Moreover,
following recovery from the severe brunt of COVID-19 infection, interstitial portions of alveoli
have been found to undergo residual scarring and further to have compromised air exchange.
Such alterations in the lung microenvironment and associated systemic manifestations have been
recognized to occur due to the extensive release of cytokines. The mortality rate increases with advancing
age and in individuals with underlying co-morbidity. Presently, there is no availability of
specific antiviral therapy or any other definitive modality to counter this progressive worsening.
However, we believe principles and advancing cell-based therapy may prove fruitful in subjugating
such reported worsening in these patients. This article reviews eminent knowledge and relevant advancements
about the amelioration of lung damage due to COVID-19 infection using adipose tissue-
derived - total stromal fraction (TSF).
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Affiliation(s)
- Niraj Kumar Jha
- Department of Biotechnology, School of Engineering & Technology, Sharda University, Greater Noida,
Uttar Pradesh, India
| | - Mohammad Amjad Kamal
- King Fahd Medical Research
Center, King Abdulaziz University, Jeddah, Saudi Arabia
- West China School of Nursing / Institutes for Systems Genetics,
Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University,
Chengdu 610041, Sichuan, China
- Enzymoics, Novel Global Community Educational Foundation, Hebersham, NSW
2770, Australia
| | - Kavindra Kumar Kesari
- Department of Applied Physics, School of Science, Aalto University, Espoo, Finland
- Enzymoics, Novel Global Community Educational Foundation, Hebersham, NSW
2770, Australia
| | - Saurabh Kumar Jha
- Department of Biotechnology, School of Engineering & Technology, Sharda University, Greater Noida,
Uttar Pradesh, India
- International Association of Stem Cell and Regenerative Medicine (IASRM), New Delhi, India
- Enzymoics, Novel Global Community Educational Foundation, Hebersham, NSW
2770, Australia
| | - Madhan Jeyaraman
- Department of Orthopaedics, School of Medical Sciences and Research, Sharda University, Greater Noida, Uttar
Pradesh, India
- Department of Biotechnology, School of Engineering & Technology, Sharda University, Greater Noida,
Uttar Pradesh, India
- International Association of Stem Cell and Regenerative Medicine (IASRM), New Delhi, India
- Orthopaedic Research Group, Coimbatore, Tamil Nadu, India
| | - Sathish Muthu
- Department of Biotechnology, School of Engineering & Technology, Sharda University, Greater Noida,
Uttar Pradesh, India
- International Association of Stem Cell and Regenerative Medicine (IASRM), New Delhi, India
- Orthopaedic Research Group, Coimbatore, Tamil Nadu, India
- Department of Orthopaedics, Government
Dindigul Medical College and Hospital, Dindigul, Tamil Nadu, India
| | - Rashmi Jain
- School of Medical Sciences and Research, Sharda
University, Greater Noida, Uttar Pradesh, India
| | - Ajay Shringeri Satish
- International Association of Stem Cell and Regenerative Medicine (IASRM), New Delhi, India
- Department of Orthopaedics, Sri Devaraj Urs Medical College,
Kolar, Karnataka, India
| | - Neha Garg
- International Association of Stem Cell and Regenerative Medicine (IASRM), New Delhi, India
- Department of Obstetrics & Gynaecology, Lady Hardinge Medical College, New Delhi, India
| | - Prabhu Chandra Mishra
- International Association of Stem Cell and Regenerative Medicine (IASRM), New Delhi, India
| | - Kumari Swati
- Department of Biotechnology, School of Life Science, Mahatma Gandhi Central University, Motihari, Bihar, India
| | - Anand Parkash
- Department of Biotechnology, School of Life Science, Mahatma Gandhi Central University, Motihari, Bihar, India
| | - Shreesh Ojha
- Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab, Emirates
University, Abu Dhabi, United Arab Emirates
| | | | - Dhruv Kumar
- Amity Institute of Molecular Medicine and Stem Cell Research, Amity University, Noida, India
| | - Janne Ruokolainen
- Department of Applied Physics, School of Science, Aalto University, Espoo, Finland
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49
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Nepal S, Venkataram A, Mysore V. The Role of Adipose Tissue in Hair Regeneration: A Potential Tool for Management? J Cutan Aesthet Surg 2021; 14:295-304. [PMID: 34908771 PMCID: PMC8611710 DOI: 10.4103/jcas.jcas_47_19] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
Human adipose tissue (AT) is a rich and easily harvestable source of stem cells and various growth factors (GFs). It has been widely used hitherto for facial rejuvenation and volumization. Increasing evidence shows that dermal adipocytes are intricately associated with hair follicles (HFs) and may be necessary to drive follicular stem cell activation. Early published data have shown encouraging preliminary results for the use of adipocytes and their stem cells as a treatment option for hair growth. The aim of this review study is to analyze published literature on the effect of fat on hair growth and to summarize the current evidence.
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Affiliation(s)
- Suman Nepal
- The Venkat Center for Skin, ENT and Plastic Surgery, Bengaluru, Karnataka, India
| | - Aniketh Venkataram
- The Venkat Center for Skin, ENT and Plastic Surgery, Bengaluru, Karnataka, India
| | - Venkataram Mysore
- The Venkat Center for Skin, ENT and Plastic Surgery, Bengaluru, Karnataka, India
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50
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Verpaele A, Tonnard P, Ghiasloo M. Invited Discussion on: "Nanofat Cell-Mediated Anti-Aging Therapy: Evidence-Based Analysis of Efficacy and an Update of Stem Cell Facelift" by Bishara Atiyeh, Fadi Ghieh, Ahmad Oneisi. Aesthetic Plast Surg 2021; 45:2948-2951. [PMID: 34529105 DOI: 10.1007/s00266-021-02572-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2021] [Accepted: 09/02/2021] [Indexed: 11/28/2022]
Affiliation(s)
- Alexis Verpaele
- Tonnard and Verpaele Plastic Surgery Associates, Coupure 164 c/d, 9000, Ghent, Belgium.
| | - Patrick Tonnard
- Tonnard and Verpaele Plastic Surgery Associates, Coupure 164 c/d, 9000, Ghent, Belgium
| | - Mohammad Ghiasloo
- Department of Plastic and Reconstructive Surgery, Ghent University Hospital, Corneel Heymanslaan 10, Entrance 12, Route 1281, 9000, Ghent, Belgium
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