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Maeda T, Sobajima S, Matsumoto T, Tsubosaka M, Matsushita T, Iwaguro H, Kuroda R. Comparison of short-term clinical outcomes of intra-articular injection of micro-fragmented adipose tissue and stromal vascular fraction cells for knee osteoarthritis treatment: A retrospective single-center cohort study. Regen Ther 2025; 29:91-99. [PMID: 40129683 PMCID: PMC11932757 DOI: 10.1016/j.reth.2025.02.013] [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: 01/23/2025] [Revised: 02/15/2025] [Accepted: 02/27/2025] [Indexed: 03/26/2025] Open
Abstract
Background Stromal vascular fraction (SVF) cells and micro-fragmented adipose tissue (MFAT) have potential for treating knee osteoarthritis (OA), but their efficacy has not been compared. This study aimed to compare the clinical outcomes of SVF and MFAT for knee OA. We hypothesized that SVF provides stronger short-term effects, while MFAT offers more sustained benefits. Methods A retrospective single-center cohort study was conducted on patients with knee OA, with 36 SVF and 36 MFAT cases selected through propensity score matching between September 2017 and February 2022. Patients with KL grades I-IV varus knee OA, significant pain (VAS ≥40), and functional impairment despite conservative treatments were included. Those with knee trauma, severe bony defects, infections, genu valgus, osteonecrosis, rheumatoid arthritis, or severe deformities were excluded. Clinical outcomes were assessed using the visual analog scale, KOOS, knee range of motion, extension/flexion strength, and MRI T2 mapping. Results SVF and MFAT groups demonstrated significant improvements in VAS (p < 0.01 for both groups). Both groups showed notable improvements in extension angle, extension/flexion muscle strength, and KOOS, with no significant differences between them. However, the MFAT group demonstrated significantly greater improvement in flexion angle compared to the SVF group (p = 0.03). No serious adverse events were reported. T2 mapping showed significant improvements in cartilage quality in both groups, with the MFAT group demonstrating superior improvements in specific lateral regions. Responder rate in SVF group initially improved but declined over time; however, the MFAT group showed sustained improvement from six months onward. Conclusion T2 mapping revealed that MFAT had better cartilage preservation than that of SVF cells in less-loaded areas, with a potentially longer-lasting therapeutic effect. These findings offer important insights for clinicians to tailor treatment strategies based on patient needs and disease progression.
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Affiliation(s)
- Takuma Maeda
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
- Department of Orthopaedic Surgery, Sobajima Clinic, Higashiosaka, Japan
| | - Satoshi Sobajima
- Department of Orthopaedic Surgery, Sobajima Clinic, Higashiosaka, Japan
| | - Tomoyuki Matsumoto
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Masanori Tsubosaka
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Takehiko Matsushita
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Hideki Iwaguro
- Department of Orthopaedic Surgery, Sobajima Clinic, Higashiosaka, Japan
| | - Ryosuke Kuroda
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
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Zhang H, Felthaus O, Prantl L. Adipose Tissue-Derived Therapies for Osteoarthritis: Multifaceted Mechanisms and Clinical Prospects. Cells 2025; 14:669. [PMID: 40358193 PMCID: PMC12071781 DOI: 10.3390/cells14090669] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2025] [Revised: 04/28/2025] [Accepted: 05/01/2025] [Indexed: 05/15/2025] Open
Abstract
Osteoarthritis (OA) is a degenerative joint disease that significantly impacts quality of life and poses a growing economic burden. Adipose tissue-derived therapies, including both cell-based and cell-free products, have shown promising potential in promoting cartilage repair, modulating inflammation, and improving joint function. Recent studies and clinical trials have demonstrated their regenerative effects, highlighting their feasibility as a novel treatment approach for OA. This review summarises the therapeutic mechanisms and latest advancements in adipose tissue-derived therapies, providing insights into their clinical applications and future prospects.
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Affiliation(s)
- Hanwen Zhang
- Department of Plastic, Hand and Reconstructive Surgery, University Hospital Regensburg, Franz-Josef-Strauß Allee 11, 93053 Regensburg, Germany
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De Francesco F, Sbarbati A, Sierra LAQ, Zingaretti N, Sarmadian Z, Parodi PC, Ricci G, Riccio M, Mobasheri A. Anatomy, Histology, and Embryonic Origin of Adipose Tissue: Insights to Understand Adipose Tissue Homofunctionality in Regeneration and Therapies. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2025; 1474:53-78. [PMID: 39107527 DOI: 10.1007/5584_2024_801] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
Abstract
Preadipocytes are formed during the 14th and 16th weeks of gestation. White adipose tissue, in particular, is generated in specific areas and thereby assembles after birth, rapidly increasing following the propagation of adipoblasts, which are considered the preadipocyte cell precursors. The second trimester of gestation is a fundamental phase of adipogenesis, and in the third trimester, adipocytes, albeit small may be present within the main deposition areas. In the course of late gestation, adipose tissue develops in the foetus and promotes the synthesis of large amounts of uncoupling protein 1, in similar quantities relative to differentiated brown adipose tissue. In mammals, differentiation occurs in two functionally different types of adipose cells: white adipose cells resulting from lipid storage and brown adipose cells from increased metabolic energy consumption. During skeletogenesis, synovial joints develop through the condensation of mesenchymal cells, which forms an insertional layer of flattened cells that umlaut skeletal elements, by sharing the same origin in the development of synovium. Peri-articular fat pads possess structural similarity with body subcutaneous white adipose tissue; however, they exhibit a distinct metabolic function due to the micro-environmental cues in which they are embedded. Fat pads are an important component of the synovial joint and play a key role in the maintenance of joint homeostasis. They are also implicated in pathological states such as osteoarthritis.In this paper we explore the therapeutic potential of adipocyte tissue mesenchymal precursor-based stem cell therapy linking it back to the anatomic origin of adipose tissue.
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Affiliation(s)
- Francesco De Francesco
- Department of Reconstructive Surgery and Hand Surgery, AOU Ospedali Riuniti delle Marche, Ancona, Italy
| | - Andrea Sbarbati
- Department of Neuroscience, Biomedicine and Movement, Human Anatomy and Histology Section, University of Verona, Verona, Italy
| | | | - Nicola Zingaretti
- Department of Medical Area (DAME), Clinic of Plastic and Reconstructive Surgery, Academic Hospital of Udine, University of Udine, Udine, Italy
| | - Zahra Sarmadian
- Research Unit of Health Sciences and Technology, Faculty of Medicine, University of Oulu, Oulu, Finland
| | - Pier Camillo Parodi
- Department of Medical Area (DAME), Clinic of Plastic and Reconstructive Surgery, Academic Hospital of Udine, University of Udine, Udine, Italy
| | - Giulia Ricci
- Department of Experimental Medicine, Università Degli Studi Della Campania "Luigi Vanvitelli", Naples, Italy
| | - Michele Riccio
- Department of Reconstructive Surgery and Hand Surgery, AOU Ospedali Riuniti delle Marche, Ancona, Italy
| | - Ali Mobasheri
- Research Unit of Health Sciences and Technology, Faculty of Medicine, University of Oulu, Oulu, Finland.
- Department of Regenerative Medicine, State Research Institute Centre for Innovative Medicine, Vilnius, Lithuania.
- Department of Joint Surgery, Sun Yat-sen University, Guangzhou, People's Republic of China.
- World Health Organization Collaborating Center for Public Health Aspects of Musculoskeletal Health and Aging, Université de Liège, Liège, Belgium.
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Zampogna B, Parisi FR, Ferrini A, Zampoli A, Papalia GF, Shanmugasundaram S, Papalia R. Safety and efficacy of autologous adipose-derived stem cells for knee osteoarthritis in the elderly population: A systematic review. J Clin Orthop Trauma 2024; 59:102804. [PMID: 39628863 PMCID: PMC11609259 DOI: 10.1016/j.jcot.2024.102804] [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: 04/19/2024] [Revised: 07/17/2024] [Accepted: 11/06/2024] [Indexed: 12/06/2024] Open
Abstract
INTRODUCTION Osteoarthritis (OA) is a progressive joint disease, and over 240 million people suffer from symptomatic OA, primarily in the knee, and mainly affects the elderly population over 65. A combination of different risk factors leads to biological changes in the microenvironments of the joints, causing cartilage overload and chondrocyte aging. Adipose-derived MSCs (ADSCs) are demonstrated to improve joint environments with an effective therapy for Knee OA. This review focused on patients over 65 years old to evaluate the effectiveness of ADSC therapies in treating KOA in elderly patients and demonstrate that complications are not higher in this cohort of patients. MATERIALS AND METHODS We conducted a bibliography search through the PubMed, Scopus, and Cochrane databases for English-language and human clinical trials published until Feb 7, 2024. We extracted the following study characteristics: Authors, year of publication, type of study, number of patients, number of knees, sex, Kellgren-Lawrence classification, culture ADSC, Number of cells injected, mean follow-up, adverse events, significant complications, and clinical outcomes data were extracted recorded and analyzed. RESULTS According to inclusion criteria, seven clinical trials on autologous adipose-derived stem cells were considered. Four studies analyzed stem cells as a stromal vascular fraction (SVF), two as ADSC cultured, and 1 study investigated the MAT procedure. All studies reported improved clinical outcomes using autologous adipose-derived stem cells, on 339 knees. Post-treatment increased KOOS, WOMAC, IKS, VAS, and Lysholm knee scores were highlighted. All studies showed an improvement in all outcomes scores, and regarding complications, only 44 knees underwent adverse events, but no significant complications were found in all the studies reported. CONCLUSIONS The current systematic review demonstrated that using autologous adipose-derived stem cells improved clinical outcomes and is effective and safe in elderly patients. Additionally, this study will encourage orthopedic surgeons not to consider surgery as the only solution in elderly patients who are refractory to treatment and do not show end-stage knee osteoarthritis. LEVEL OF EVIDENCE Level IV, systematic review of level IV studies.
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Affiliation(s)
- Biagio Zampogna
- Department of Orthopaedic and Trauma Surgery, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo, 21, 00128, Roma, Italy
- Research Unit of Orthopaedic and Trauma Surgery, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128, Roma, Italy
- BIOMORF Department, Biomedical, Dental and Morphological and Functional Images, University of Messina. A.O.U. Policlinico “G. Martino”, Messina, Italy
| | - Francesco Rosario Parisi
- Department of Orthopaedic and Trauma Surgery, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo, 21, 00128, Roma, Italy
- Research Unit of Orthopaedic and Trauma Surgery, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128, Roma, Italy
| | - Augusto Ferrini
- Department of Orthopaedic and Trauma Surgery, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo, 21, 00128, Roma, Italy
- Research Unit of Orthopaedic and Trauma Surgery, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128, Roma, Italy
| | - Andrea Zampoli
- Department of Orthopaedic and Trauma Surgery, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo, 21, 00128, Roma, Italy
- Research Unit of Orthopaedic and Trauma Surgery, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128, Roma, Italy
| | - Giuseppe Francesco Papalia
- Department of Orthopaedic and Trauma Surgery, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo, 21, 00128, Roma, Italy
- Research Unit of Orthopaedic and Trauma Surgery, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128, Roma, Italy
| | | | - Rocco Papalia
- Department of Orthopaedic and Trauma Surgery, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo, 21, 00128, Roma, Italy
- Research Unit of Orthopaedic and Trauma Surgery, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128, Roma, Italy
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Onoi Y, Matsumoto T, Anjiki K, Hayashi S, Nakano N, Kuroda Y, Tsubosaka M, Kamenaga T, Ikuta K, Tachibana S, Suda Y, Wada K, Maeda T, Saitoh A, Hiranaka T, Sobajima S, Iwaguro H, Matsushita T, Kuroda R. Human uncultured adipose-derived stromal vascular fraction shows therapeutic potential against osteoarthritis in immunodeficient rats via direct effects of transplanted M2 macrophages. Stem Cell Res Ther 2024; 15:325. [PMID: 39334434 PMCID: PMC11438128 DOI: 10.1186/s13287-024-03946-3] [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: 03/30/2024] [Accepted: 09/18/2024] [Indexed: 09/30/2024] Open
Abstract
BACKGROUND The uncultured adipose-derived stromal vascular fraction (SVF), consisting of adipose-derived stromal cells (ADSCs), M2 macrophages (M2Φ) and others, has shown therapeutic potential against osteoarthritis (OA), however, the mechanisms underlying its therapeutic effects remain unclear. Therefore, this study investigated the effects of the SVF on OA in a human-immunodeficient rat xenotransplantation model. METHODS OA model was induced in the knees of female immunodeficient rats by destabilization of the medial meniscus. Immediately after the surgery, human SVF (1 × 105), ADSCs (1 × 104), or phosphate buffered saline as a control group were transplanted into the knees. At 4 and 8 weeks postoperatively, OA progression and synovitis were analyzed by macroscopic and histological analyses, and the expression of collagen II, SOX9, MMP-13, ADAMTS-5, F4/80, CD86 (M1), CD163 (M2), and human nuclear antigen (hNA) were evaluated immunohistochemically. In vitro, flow cytometry was performed to collect CD163-positive cells as M2Φ from the SVF. Chondrocyte pellets (1 × 105) were co-cultured with SVF (1 × 105), M2Φ (1 × 104), and ADSCs (1 × 104) or alone as a control group, and the pellet size was compared. TGF-β, IL-10 and MMP-13 concentrations in the medium were evaluated using enzyme-linked immunosorbent assay. RESULTS In comparison with the control and ADSC groups, the SVF group showed significantly slower OA progression and less synovitis with higher expression of collagen II and SOX9, lower expression of MMP-13 and ADAMTS-5, and lower F4/80 and M1/M2 ratio in the synovium. Only the SVF group showed partial expression of hNA-, CD163-, and F4/80-positive cells in the rat synovium. In vitro, the SVF, M2Φ, ADSC and control groups, in that order, showed larger pellet sizes, higher TGF-β and IL-10, and lower MMP-13 concentrations. CONCLUSIONS The M2Φ in the transplanted SVF directly affected recipient tissue, enhancing the secretion of growth factors and chondrocyte-protecting cytokines, and partially improving chondrocytes and joint homeostasis. These findings indicate that the SVF is as an effective option for regenerative therapy for OA, with mechanisms different from those of ADSCs.
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Affiliation(s)
- Yuma Onoi
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Tomoyuki Matsumoto
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
| | - Kensuke Anjiki
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Shinya Hayashi
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Naoki Nakano
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Yuichi Kuroda
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Masanori Tsubosaka
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Tomoyuki Kamenaga
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Kemmei Ikuta
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Shotaro Tachibana
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Yoshihito Suda
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Kensuke Wada
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Takuma Maeda
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Akira Saitoh
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Takafumi Hiranaka
- Department of Orthopaedic Surgery and Joint Surgery Center, Takatsuki General Hospital, Osaka, Japan
| | - Satoshi Sobajima
- Department of Orthopaedic Surgery, Sobajima Clinic, Osaka, Japan
| | - Hideki Iwaguro
- Department of Orthopaedic Surgery, Sobajima Clinic, Osaka, Japan
| | - Takehiko Matsushita
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Ryosuke Kuroda
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
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Jeyaraman N, Shrivastava S, Ravi VR, Nallakumarasamy A, Pundkar A, Jeyaraman M. Understanding and controlling the variables for stromal vascular fraction therapy. World J Stem Cells 2024; 16:784-798. [PMID: 39219728 PMCID: PMC11362852 DOI: 10.4252/wjsc.v16.i8.784] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2024] [Revised: 06/13/2024] [Accepted: 07/25/2024] [Indexed: 08/26/2024] Open
Abstract
In regenerative medicine, the isolation of mesenchymal stromal cells (MSCs) from the adipose tissue's stromal vascular fraction (SVF) is a critical area of study. Our review meticulously examines the isolation process of MSCs, starting with the extraction of adipose tissue. The choice of liposuction technique, anatomical site, and immediate processing are essential to maintain cell functionality. We delve into the intricacies of enzymatic digestion, emphasizing the fine-tuning of enzyme concentrations to maximize cell yield while preventing harm. The review then outlines the filtration and centrifugation techniques necessary for isolating a purified SVF, alongside cell viability assessments like flow cytometry, which are vital for confirming the efficacy of the isolated MSCs. We discuss the advantages and drawbacks of using autologous vs allogeneic SVF sources, touching upon immunocompatibility and logistical considerations, as well as the variability inherent in donor-derived cells. Anesthesia choices, the selection between hypodermic needles vs liposuction cannulas, and the role of adipose tissue lysers in achieving cellular dissociation are evaluated for their impact on SVF isolation. Centrifugation protocols are also analyzed for their part in ensuring the integrity of the SVF. The necessity for standardized MSC isolation protocols is highlighted, promoting reproducibility and successful clinical application. We encourage ongoing research to deepen the understanding of MSC biology and therapeutic action, aiming to further the field of regenerative medicine. The review concludes with a call for rigorous research, interdisciplinary collaboration, and strict adherence to ethical and regulatory standards to safeguard patient safety and optimize treatment outcomes with MSCs.
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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, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha 442004, Maharashtra, India
| | - V R 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
| | - Aditya Pundkar
- Department of Orthopaedics, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha 442004, Maharashtra, 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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Riggle C, McLellan M, Bohlen H, Wang D. Complications of Stem Cell-Based Injections for Knee Osteoarthritis: A Systematic Review. HSS J 2024:15563316241271058. [PMID: 39564419 PMCID: PMC11572451 DOI: 10.1177/15563316241271058] [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: 03/11/2024] [Accepted: 05/27/2024] [Indexed: 11/21/2024]
Abstract
Knee osteoarthritis (OA) remains a common cause of knee pain and dysfunction. Stem cell-based injections have been widely used for the treatment of knee OA, but the types and rates of post-injection complications are not well characterized. We sought to characterize the type and severity of adverse events and quantify the frequency of adverse events associated with stem cell injections used to treat knee OA. We conducted a systematic review that followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. We searched the PubMed and the Cochrane library databases for studies on adverse events and complications associated with stem cell-based therapies used to treat knee OA published from January 2000 through June 2021. Inclusion criteria were the use of intra-articular autologous bone marrow stem cells (BMSCs) or bone marrow aspirate concentrate (BMAC), autologous adipose-derived mesenchymal stem cells (ADMSCs) including microfragmented lipoaspirate, concentrated adipose tissue, cultured stem cells, autologous stromal vascular fraction (SVF), or umbilical or placental derived stem cells in human participants. Primary data extracted from included studies were patient demographics, methods of treatment, and reported character, duration, and severity of adverse events. A total of 427 studies were screened, and 48 studies were included, including randomized controlled trials, prospective studies, and retrospective studies. Among the 1924 patients in the analysis, there was an overall 12.3% rate of transient adverse events, the most frequent being swelling and pain at the injection site. Umbilical cord-derived (51.7%) and cultured ADMSC (29.5%) injections had a significantly higher occurrence of these adverse events than BMSC and SVF injections. No other adverse events, including infection, fat embolism, or medical complications, were reported. Despite significant heterogeneity of the included studies in terms of the protocol, formulation, timing, and location of injections, the findings of this systematic review suggest that, in the short term, treatment of knee OA with autologous mesenchymal stem cell injections poses no risk of major complications (infection, sepsis, neoplasm, embolism, or death) and poses moderate risk of swelling and pain at the injection site lasting less than 4 weeks. Further long-term studies are needed to conclusively determine the safety profile of these injections.
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Affiliation(s)
- Clara Riggle
- Department of Orthopaedic Surgery, University of California, Irvine, Orange, CA, USA
| | - Maddison McLellan
- Department of Orthopaedic Surgery, University of California, Irvine, Orange, CA, USA
| | - Hunter Bohlen
- Department of Orthopaedic Surgery, University of California, Irvine, Orange, CA, USA
| | - Dean Wang
- Department of Orthopaedic Surgery, University of California, Irvine, Orange, CA, USA
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Klingenberg M, Dineva A, Hoyer A, Kaltschmidt B, Leimkühler P, Vordemvenne T, Elsner A, Wähnert D. Injection of Autologous Adipose Stromal Vascular Fraction in Combination with Autologous Conditioned Plasma for the Treatment of Advanced Knee Osteoarthritis Significantly Improves Clinical Symptoms. J Clin Med 2024; 13:3031. [PMID: 38892743 PMCID: PMC11172752 DOI: 10.3390/jcm13113031] [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: 03/22/2024] [Revised: 05/10/2024] [Accepted: 05/18/2024] [Indexed: 06/21/2024] Open
Abstract
(1) Background: Osteoarthritis (OA) is the most common joint disease in the world. It is chronic, systemic, progressive and disabling. Orthobiologics have the potential to positively alter the course of this disease. Therefore, the aim of this study is to evaluate the efficacy of SVF/ACP in the treatment of advanced osteoarthritis of the knee in an unfiltered patient population. We hypothesize that this therapy can improve the symptoms associated with osteoarthritis of the knee. We also hypothesize that there are patient-related factors that influence the efficacy of therapy. (2) Methods: Two hundred and thirteen patients with moderate to severe OA of the knee and SVF/ACP injection were recruited for this study. Patients were excluded if they did not provide informed consent or were not receiving SVF/ACP therapy. Pain, function, symptoms and quality of life were assessed using standardized scores (KOOS, WOMAC) before and after treatment. (3) Results: The VAS pain score was significantly reduced by at least 30% (p < 0.001). Knee function, as measured by the KOOS daily activity and sport scores, showed significant increases of 21% and 45%, respectively, at 6 months (p < 0.04). (4) Conclusions: Treatment of knee OA with SVF/ACP injection positively modifies the disease by significantly reducing pain and improving function.
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Affiliation(s)
| | - Antoniya Dineva
- Biostatistics and Medical Biometry, Medical School OWL, Bielefeld University, Universitätsstrasse 25, 33615 Bielefeld, Germany; (A.D.); (A.H.)
| | - Annika Hoyer
- Biostatistics and Medical Biometry, Medical School OWL, Bielefeld University, Universitätsstrasse 25, 33615 Bielefeld, Germany; (A.D.); (A.H.)
| | - Barbara Kaltschmidt
- Department of Cell Biology, Bielefeld University, Universitätsstrasse 25, 33615 Bielefeld, Germany;
- Molecular Neurobiology, Bielefeld University, Universitätsstrasse 25, 33615 Bielefeld, Germany
| | - Philipp Leimkühler
- Department of Trauma and Orthopaedic Surgery, Medical School and University Medical Center OWL, Protestant Hospital of the Bethel Foundation, Bielefeld University, Burgsteig 13, 33617 Bielefeld, Germany; (P.L.); (T.V.); (D.W.)
- DIOSS (German Institute for Orthopaedics, Osteopathy and Sports Medicine), Lipper Hellweg 10, 33604 Bielefeld, Germany;
| | - Thomas Vordemvenne
- Department of Trauma and Orthopaedic Surgery, Medical School and University Medical Center OWL, Protestant Hospital of the Bethel Foundation, Bielefeld University, Burgsteig 13, 33617 Bielefeld, Germany; (P.L.); (T.V.); (D.W.)
- DIOSS (German Institute for Orthopaedics, Osteopathy and Sports Medicine), Lipper Hellweg 10, 33604 Bielefeld, Germany;
| | - Andreas Elsner
- DIOSS (German Institute for Orthopaedics, Osteopathy and Sports Medicine), Lipper Hellweg 10, 33604 Bielefeld, Germany;
- Orthopedic Joint Practice at Bültmannshof, Kurt-Schumacher-Straße 17, 33615 Bielefeld, Germany
| | - Dirk Wähnert
- Department of Trauma and Orthopaedic Surgery, Medical School and University Medical Center OWL, Protestant Hospital of the Bethel Foundation, Bielefeld University, Burgsteig 13, 33617 Bielefeld, Germany; (P.L.); (T.V.); (D.W.)
- DIOSS (German Institute for Orthopaedics, Osteopathy and Sports Medicine), Lipper Hellweg 10, 33604 Bielefeld, Germany;
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Yuan C, Song W, Jiang X, Wang Y, Li C, Yu W, He Y. Adipose-derived stem cell-based optimization strategies for musculoskeletal regeneration: recent advances and perspectives. Stem Cell Res Ther 2024; 15:91. [PMID: 38539224 PMCID: PMC10976686 DOI: 10.1186/s13287-024-03703-6] [Citation(s) in RCA: 11] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2023] [Accepted: 03/19/2024] [Indexed: 04/23/2025] Open
Abstract
Musculoskeletal disorders are the leading causes of physical disabilities worldwide. The poor self-repair capacity of musculoskeletal tissues and the absence of effective therapies have driven the development of novel bioengineering-based therapeutic approaches. Adipose-derived stem cell (ADSC)-based therapies are being explored as new regenerative strategies for the repair and regeneration of bone, cartilage, and tendon owing to the accessibility, multipotency, and active paracrine activity of ADSCs. In this review, recent advances in ADSCs and their optimization strategies, including ADSC-derived exosomes (ADSC-Exos), biomaterials, and genetic modifications, are summarized. Furthermore, the preclinical and clinical applications of ADSCs and ADSC-Exos, either alone or in combination with growth factors or biomaterials or in genetically modified forms, for bone, cartilage, and tendon regeneration are reviewed. ADSC-based optimization strategies hold promise for the management of multiple types of musculoskeletal injuries. The timely summary and highlights provided here could offer guidance for further investigations to accelerate the development and clinical application of ADSC-based therapies in musculoskeletal regeneration.
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Affiliation(s)
- Chenrui Yuan
- Department of Orthopedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China
| | - Wei Song
- Department of Orthopedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China
| | - Xiping Jiang
- Department of Orthopedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China
| | - Yifei Wang
- Department of Orthopedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China
| | - Chenkai Li
- Department of Orthopedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China
| | - Weilin Yu
- Department of Orthopedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China
| | - Yaohua He
- Department of Orthopedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China.
- Department of Orthopedics, Jinshan Branch of Shanghai Sixth People's Hospital Affiliated to Shanghai University of Medicine & Health Sciences, Shanghai, 201500, China.
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10
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Ehioghae M, Vippa TK, Askins D, Slusarczyk S, Bobo E, Montoya A, Anderson D, Robinson CL, Kaye AD, Urits I. Exploring Orthopedic Stem-Cell Approaches for Osteoarthritis Management: Current Trends and Future Horizons. Curr Pain Headache Rep 2024; 28:27-35. [PMID: 38010488 DOI: 10.1007/s11916-023-01191-6] [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] [Accepted: 11/20/2023] [Indexed: 11/29/2023]
Abstract
PURPOSE OF REVIEW Osteoarthritis (OA) is a prevalent and debilitating condition characterized by joint degeneration and pain. Current treatment options aim to alleviate symptoms and slow disease progression but lack curative potential. Stem cell therapies have emerged as a promising alternative. This article explores the epidemiology, pathophysiology, clinical manifestations of hip and knee OA, and the evolving role of stem cell therapies in their treatment. RECENT FINDINGS The global prevalence of OA, with knee OA being the most common form, has fueled the demand for stem cell therapies. Despite limited robust evidence supporting their efficacy, clinical trials investigating stem-cell treatments for OA have reported encouraging radiological and clinical improvements. Stem cell therapies offer potential disease-modifying benefits through immunomodulatory actions, growth factor secretion, and chondrogenic capabilities. Adipose-derived mesenchymal stem cells (ADMSCs) have shown promise in clinical trials for OA treatment, offering potential pain relief and functional improvement. ADMSCs possess advantages such as accessibility and a favorable safety profile, making them a viable option for OA management. Although other stem-cell types, including human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs), have been used in OA treatment, ADMSCs have demonstrated superior outcomes. By providing a comprehensive overview of the evolving landscape of stem cell therapies for hip and knee OA, this article highlights the potential of stem-cell treatments to address the limitations of current therapies. However, further research is required to establish their long-term efficacy, identify optimal stem-cell types, and develop standardized protocols.
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Affiliation(s)
| | | | | | | | - Elena Bobo
- Tulane University School of Medicine, New Orleans, USA
| | - Alexis Montoya
- University of Arizona College of Medicine-Phoenix, Phoenix, USA
| | | | | | - Alan D Kaye
- Louisiana State University Health Shreveport, Shreveport, USA
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11
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Onoi Y, Matsumoto T, Sobajima S, Tsubosaka M, Hayashi S, Matsushita T, Iwaguro H, Kuroda R. Clinical use of autologous adipose-derived stromal vascular fraction cell injections for hip osteoarthritis. Regen Ther 2023; 24:94-102. [PMID: 37363753 PMCID: PMC10285449 DOI: 10.1016/j.reth.2023.06.006] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Revised: 05/04/2023] [Accepted: 06/07/2023] [Indexed: 06/28/2023] Open
Abstract
Introduction Currently, studies on adipose-derived stromal vascular fraction (SVF) cells are attracting increasing attention because they have the potential to differentiate into a subset of cell types, such as bone marrow-derived mesenchymal stromal cells (MSCs), and are easier to harvest than MSCs, thus making them easier to apply clinically. This study evaluated the short-term clinical outcomes of SVF cell therapy for hip osteoarthritis (OA). Methods Forty-two patients were enrolled in this study; these patients received a single injection comprising an average of 3.8 (standard deviation [SD], ±1.3) × 107 SVF cells into the hip joint. All patients were followed-up for at least 6 months. The mean age of the patients was 60.2 years (SD, ±9.4 years). Kellgren-Lawrence (KL) grades II, III, and IV based on radiography were 13, 13, and 16 patients, respectively. SVF cells were obtained from the subcutaneous fat of the abdomen or breech using a Celution® 800/CRS system. The average cell viability of SVF cells was 90.8% (SD, ±2.8%). Clinical assessments were performed using the Harris Hip Score (HHS), Japanese Orthopaedic Association Hip Disease Evaluation Questionnaire (JHEQ) score, and visual analog scale (VAS) score to evaluate pain. Images were evaluated using radiography, and T2 mapping values were obtained using a 1.5-T magnetic resonance imaging system. These clinical and imaging assessments were followed from preoperatively to 6 months postoperatively. Results The HHS, JHEQ score, and VAS score improved significantly from 22.5 (SD, ±16.6), 26.6 (SD, ±11.3), and 75.5 (SD, ±15.8) preoperatively to 46.8 (SD, ±27.2), 39.4 (SD, ±19.7), and 46.5 (SD, ±27.9), respectively, at 6 months postoperatively. KL grade II showed significant improvement in clinical outcome from preoperative to postoperative, while KL grade IV showed slight or little improvement. The center edge angle, acetabular head index on the radiographs, and T2 mapping values did not change significantly from preoperatively to 6 months postoperatively. Conclusions SVF cell injection in the hip joint showed good short-term clinical efficacy for reducing hip OA symptoms. SVF cell therapy is thus an innovative and effective treatment for hip OA.
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Affiliation(s)
- Yuma Onoi
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Tomoyuki Matsumoto
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Satoshi Sobajima
- Department of Orthopaedic Surgery, Sobajima Clinic, Osaka, Japan
| | - Masanori Tsubosaka
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Shinya Hayashi
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Takehiko Matsushita
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Hideki Iwaguro
- Department of Orthopaedic Surgery, Sobajima Clinic, Osaka, Japan
| | - Ryosuke Kuroda
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
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12
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Ferreira MY, Carvalho Junior JDC, Ferreira LM. Evaluating the quality of studies reporting on clinical applications of stromal vascular fraction: A systematic review and proposed reporting guidelines (CLINIC-STRA-SVF). Regen Ther 2023; 24:332-342. [PMID: 37662694 PMCID: PMC10474569 DOI: 10.1016/j.reth.2023.08.003] [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: 06/14/2023] [Revised: 07/26/2023] [Accepted: 08/13/2023] [Indexed: 09/05/2023] Open
Abstract
Background The stromal vascular fraction (SVF) has been widely explored in a number of therapeutic applications in several specialties. Its therapeutic potential is being increasingly demonstrated, although its mechanism of action is still unclear. Objective To evaluate the quality of studies reporting on clinical applications of SVF. Method This is a systematic literature review that followed the PRISMA guidelines with the search of the studies from December 1, 2012, to December 1, 2022, in the following databases: MEDLINE, LILACS and EMBASE. The level of evidence of the studies was assessed using the GRADE system, and the rigor used in the publication of the results was assessed in relation to adherence to the guidelines indicated by the EQUATOR Network Group. The CLINIC - STRA-SVF reporting guideline was developed after the completion of this systematic review. Results A total of 538 articles were found, and 77 articles were selected after reading the titles and abstracts and removing duplicates. Then, 15 studies were removed for not meeting the inclusion criteria, leaving 62 studies. The CLINIC - STRA-SVF was developed and consists of 33 items and two tables. Conclusion There is scientific evidence, although mostly with a low level of evidence, that the use of SVF in clinical applications is safe and effective. The information published in these studies should be standardized, and the CLINIC - STRA-SVF reporting guideline proposed in this study may assist in the design, conduct, recording and reporting of clinical trials and others clinical studies involving the SVF.
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Affiliation(s)
- Marcio Yuri Ferreira
- Translational Surgery Graduate Program of Universidade Federal de São Paulo - Unifesp, São Paulo, SP, Brazil
| | | | - Lydia Masako Ferreira
- Plastic Surgery Division, Universidade Federal de São Paulo - Escola Paulista de Medicina, SP, Brazil
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13
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Tantuway V, Thomas W, Parikh MB, Sharma R, Jeyaraman N, Jeyaraman M. Clinical Outcome of Minimally Manipulated, Mechanically Isolated Autologous Adipose Tissue-Derived Stromal Vascular Fraction (Sahaj Therapy®) in Knee Osteoarthritis-Randomized Controlled Trial. Indian J Orthop 2023; 57:1646-1658. [PMID: 37766954 PMCID: PMC10519910 DOI: 10.1007/s43465-023-00981-9] [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: 06/19/2023] [Accepted: 08/18/2023] [Indexed: 09/29/2023]
Abstract
Introduction Regenerative therapy has shown promising results in the treatment of osteoarthritis (OA) knee with Kellgren-Lawrence (KL) Grades I-III. We compared the safety, efficacy, functional, and clinical outcomes of intra-articular implantation of autologous adipose tissue-derived stromal vascular fraction (SVF) isolated using direct ultrasonic cavitation (Sahaj therapy-Cell Innovation Patented Technology) and saline injection in knee osteoarthritis. Materials and Methods The present prospective observational study was conducted over 3 years. We enrolled 120 patients in our study, where four patients got excluded as they did not meet the inclusion criteria. The remaining 116 patients were randomized into two groups, one with autologous adipose tissue-derived SVF and the other group with saline injection. A comparison of mean KOOS and VAS scores at different follow-ups was done using Paired 't' test. A p value of < 0.05 was considered significant. Results The results show that the SVF group had significantly higher KOOS scores (78.49 ± 6.54 in the SVF group vs 59.19 ± 5.14 in the saline group), respectively (p < 0.001). Similarly, the SVF group had significantly lesser VAS scores (3.17 ± 0.94 in the SVF group vs 3.89 ± 1.04 in the saline group), respectively (p < 0.001). Conclusions Autologous adipose tissue-derived SVF is a better choice for treating knee osteoarthritis. For individuals with degenerative osteoarthritis, autologous SVF grafting in the same surgical procedure is an innovative and promising treatment modality. Even after 3 years of follow-up, the study participants with OA knee have shown a good clinical and functional outcome.
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Affiliation(s)
- Vinay Tantuway
- Department of Orthopaedics & Traumatology, Index Medical College Hospital and Research Centre, Indore, Madhya Pradesh India
| | - Wayne Thomas
- Department of Tumor Immunology, The University of Newcastle, Callaghan, Australia
| | - Mittal B. Parikh
- Department of Orthopaedics, Navjivan Hospital, Ahmedabad, Gujarat India
| | - Raj Sharma
- Sahaj Regenerative Cell Therapeutics, Indore, Madhya Pradesh India
| | - Naveen Jeyaraman
- Department of Orthopaedics, ACS Medical College and Hospital, Dr MGR Educational and Research Institute, Chennai, Tamil Nadu India
| | - Madhan Jeyaraman
- Department of Orthopaedics, ACS Medical College and Hospital, Dr MGR Educational and Research Institute, Chennai, Tamil Nadu India
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Boada-Pladellorens A, Avellanet M, Veiga A, Pagés-Bolibar E. Microfragmented Adipose Tissue versus Platelet-Rich Plasma for the Treatment of Knee Osteoarthritis: Letter to the Editor. Am J Sports Med 2023; 51:NP5-NP6. [PMID: 36749801 DOI: 10.1177/03635465221142322] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
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Fujita M, Matsumoto T, Sobajima S, Tsubosaka M, Matsushita T, Iwaguro H, Kuroda R. Clinical and Radiological Comparison of Single and Double Intra-articular Injection of Adipose-Derived Stromal Vascular Fraction for Knee Osteoarthritis. Cell Transplant 2023; 32:9636897231190175. [PMID: 37551027 PMCID: PMC10411282 DOI: 10.1177/09636897231190175] [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: 05/16/2023] [Revised: 06/27/2023] [Accepted: 07/11/2023] [Indexed: 08/09/2023] Open
Abstract
The aim of the article is to compare the clinical and radiological outcomes between single and double stromal vascular fraction (SVF) cell injections in patients with knee osteoarthritis (OA). We included 54 patients treated for varus knee OA with intra-articular SVF cell injection. They were divided into two groups: those who received one injection and those who received two. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, knee range of motion, and knee muscle force were assessed at baseline and 3, 6, 12, and 24 months after the first injection. The preoperative hip-knee-ankle (HKA) angle was evaluated using plain radiographs, and T2 mapping values were assessed. The total WOMAC score improved significantly in the single injection group from 3 to 24 months, but the total WOMAC score in the double injection group improved significantly at 24 months. The T2 mapping values in both the groups improved, with a significant difference at 12 months. The preoperative mean HKA angle and the correlation coefficients between the HKA angle and the total WOMAC score and between the HKA angle and the T2 mapping value of the medial femur were significant. In conclusion, double injections may provide more satisfactory treatment outcomes in patients with severe varus knee alignment. This clinical trial is registered in the Japanese Ministry of Health, Labour and Welfare (URL: https://saiseiiryo.mhlw.go.jp/published_plan/index/2) with the registration name "Cell transplantation therapy for osteoarthritis using autologous subcutaneous adipose tissue-derived regenerative (stem) cells (ADRCs)," and the registration number was "PB5160012."
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Affiliation(s)
- Masahiro Fujita
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Tomoyuki Matsumoto
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Satoshi Sobajima
- Department of Orthopaedic Surgery, Sobajima Clinic, Higashiosaka, Japan
| | - Masanori Tsubosaka
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Takehiko Matsushita
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Hideki Iwaguro
- Department of Orthopaedic Surgery, Sobajima Clinic, Higashiosaka, Japan
| | - Ryosuke Kuroda
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
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16
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Molnar V, Pavelić E, Jeleč Ž, Brlek P, Matišić V, Borić I, Hudetz D, Rod E, Vidović D, Starčević N, Čemerin M, Karli DC, Primorac D. Results of Treating Mild to Moderate Knee Osteoarthritis with Autologous Conditioned Adipose Tissue and Leukocyte-Poor Platelet-Rich Plasma. J Pers Med 2022; 13:jpm13010047. [PMID: 36675708 PMCID: PMC9864413 DOI: 10.3390/jpm13010047] [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: 10/26/2022] [Revised: 12/05/2022] [Accepted: 12/21/2022] [Indexed: 12/28/2022] Open
Abstract
Knee osteoarthritis (KOA) is one of the most common musculoskeletal disorders. Much progress has been made in regenerative medicine for the symptomatic treatment of KOA, including products containing stromal vascular fraction (SVF) and platelet-rich plasma (PRP). The aim of this study was to evaluate clinical and radiological findings after the application of autologous conditioned adipose tissue (ACA) and leukocyte-poor PRP (LP-PRP) in patients with mild to moderate KOA. A total of 16 patients (eight male and eight female) with changes related to KOA on the magnetic resonance imaging (MRI), but without severe osteophytosis, full-thickness cartilage loss, or subchondral bone involvement were included in this study. Patients received an intraarticular, ultrasound-guided injection of ACA and LP-PRP. Clinical scores, including a visual analog scale for pain (VAS), Knee Injury and Osteoarthritis Outcome Score (KOOS), and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were evaluated at baseline and at the three and six month follow-ups showing a statistically significant improvements at three and six months post-intervention. Furthermore, the delayed gadolinium-enhanced MRI of the cartilage (dGEMRIC) indices were evaluated at baseline and at the three and six month follow-ups showing no significant changes after treatment with ACA and LP-PRP, which were actually equal to the dGEMRIC indices measured in the control group (hyaluronic acid applied in contralateral knees without osteoarthritis). ACA with LP-PRP presents a viable minimally invasive therapeutic option for the clinical improvement of mild to moderate KOA. However, MFAT produced by different systems is likely to differ in cellular content, which can directly affect the paracrine effect (cytokine secretion) of mesenchymal stem cells and consequently the regeneration process.
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Affiliation(s)
- Vilim Molnar
- St. Catherine Specialty Hospital, 10000 Zagreb, Croatia
- Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, 31000 Osijek, Croatia
| | | | - Željko Jeleč
- St. Catherine Specialty Hospital, 10000 Zagreb, Croatia
- Department of Nursing, University North, 42000 Varaždin, Croatia
| | - Petar Brlek
- St. Catherine Specialty Hospital, 10000 Zagreb, Croatia
| | - Vid Matišić
- St. Catherine Specialty Hospital, 10000 Zagreb, Croatia
| | - Igor Borić
- St. Catherine Specialty Hospital, 10000 Zagreb, Croatia
- School of Medicine, University of Split, 21000 Split, Croatia
- Department of Health Studies, University of Split, 21000 Split, Croatia
| | - Damir Hudetz
- St. Catherine Specialty Hospital, 10000 Zagreb, Croatia
- Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, 31000 Osijek, Croatia
- Department for Traumatology and Orthopaedics, University Hospital Dubrava, 10000 Zagreb, Croatia
| | - Eduard Rod
- St. Catherine Specialty Hospital, 10000 Zagreb, Croatia
| | - Dinko Vidović
- St. Catherine Specialty Hospital, 10000 Zagreb, Croatia
- Clinic for Traumatology, University Hospital “Sisters of Mercy”, 10000 Zagreb, Croatia
- School of Dental Medicine, University of Zagreb, 10000 Zagreb, Croatia
| | | | - Martin Čemerin
- School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
| | | | - Dragan Primorac
- St. Catherine Specialty Hospital, 10000 Zagreb, Croatia
- Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, 31000 Osijek, Croatia
- School of Medicine, University of Split, 21000 Split, Croatia
- School of Medicine, Faculty of Dental Medicine and Health, Josip Juraj Strossmayer University Osijek, 31000 Osijek, Croatia
- Medical School, University of Rijeka, 51000 Rijeka, Croatia
- Medical School, University of Mostar, 88000 Mostar, Bosnia and Herzegovina
- Eberly College of Science, Penn State University, 517 Thomas St., State College, PA 16803, USA
- The Henry C Lee College of Criminal Justice & Forensic Sciences, University of New Haven, West Haven, CT 06516, USA
- Medical School REGIOMED, 96450 Coburg, Germany
- Correspondence:
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17
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Momoi Y, Saita Y, Nagao M, Kobayashi Y, Nakajima R, Uchino S, Wakayama T, Nishio H, Fukusato S, Wakana S, Tomura J, Kobayashi K, Yoshida K, Kaneko H, Kubota M, Ishijima M. Study protocol for a randomised placebo controlled trial of platelet-rich plasma injection to prevent post-traumatic knee osteoarthritis after anterior cruciate ligament reconstruction. BMJ Open 2022; 12:e061484. [PMID: 36414304 PMCID: PMC9685167 DOI: 10.1136/bmjopen-2022-061484] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
INTRODUCTION The elevated cytokine levels in patients suffering from anterior cruciate ligament (ACL) rupture may lead to acute post-traumatic arthritis (APTA) and post-traumatic osteoarthritis (PTOA). Due to its chondrogenerative and anti-inflammatory effect, platelet-rich plasma (PRP) therapy is expected to show a positive outcome in APTA and PTOA. The proposed trial aims to quantitatively measure the efficacy of PRP injection in arresting post-traumatic cartilage degeneration among patients after ACL reconstruction. METHODS AND ANALYSIS This will be a single-blind, randomised, prospective, controlled clinical trial designed following the Consolidated Standards of Reporting Trials guidelines. After ACL reconstruction, 80 patients will be randomised to receive either leucocyte-poor PRP injection after joint aspiration or a placebo control group receiving only joint aspiration. Participants (age 20-49 years) will be those who have undergone ACL reconstruction within the past 2 weeks with a body mass index<35 and Kellgren Lawrence osteoarthritis grade<2. The primary outcome will include MRI-T2 values of knee cartilage at 6 months. The secondary outcomes will include pain assessment by Visual Analogue Scale, Knee injury and Osteoarthritis Outcome Score, blood and urine test, physical findings, measurements for muscle strength and joint stability. ETHICS AND DISSEMINATION The study was approved by The Independent Ethics Committee for Clinical Trials of the Japanese Association for the Promotion of State-of-the-Art Medicine. Results of the trial and each of the outcomes will be shared via conferences and publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER jRCTb030200391.
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Affiliation(s)
- Yasumasa Momoi
- Departments of Orhopedics, Faculty of Medicine, Juntendo University, Bunkyo-ku, Tokyo, Japan
| | - Yoshitomo Saita
- Departments of Orhopedics, Faculty of Medicine, Juntendo University, Bunkyo-ku, Tokyo, Japan
- Department of Sports and Regenerative Medicine, Faculty of Medicine, Juntendo University, Bunkyo-ku, Tokyo, Japan
| | - Masashi Nagao
- Departments of Orhopedics, Faculty of Medicine, Juntendo University, Bunkyo-ku, Tokyo, Japan
| | - Yohei Kobayashi
- Departments of Orhopedics, Faculty of Medicine, Juntendo University, Bunkyo-ku, Tokyo, Japan
| | - Ryosuke Nakajima
- Departments of Orhopedics, Faculty of Medicine, Juntendo University, Bunkyo-ku, Tokyo, Japan
| | - Sayuri Uchino
- Departments of Orhopedics, Faculty of Medicine, Juntendo University, Bunkyo-ku, Tokyo, Japan
| | - Takanori Wakayama
- Departments of Orhopedics, Faculty of Medicine, Juntendo University, Bunkyo-ku, Tokyo, Japan
| | - Hirofumi Nishio
- Departments of Orhopedics, Faculty of Medicine, Juntendo University, Bunkyo-ku, Tokyo, Japan
| | - Shin Fukusato
- Departments of Orhopedics, Faculty of Medicine, Juntendo University, Bunkyo-ku, Tokyo, Japan
| | - Suguru Wakana
- Departments of Orhopedics, Faculty of Medicine, Juntendo University, Bunkyo-ku, Tokyo, Japan
| | - Jun Tomura
- Departments of Orhopedics, Faculty of Medicine, Juntendo University, Bunkyo-ku, Tokyo, Japan
| | - Keiji Kobayashi
- Departments of Orhopedics, Faculty of Medicine, Juntendo University, Bunkyo-ku, Tokyo, Japan
| | - Keiichi Yoshida
- Departments of Orhopedics, Faculty of Medicine, Juntendo University, Bunkyo-ku, Tokyo, Japan
| | - Haruka Kaneko
- Departments of Orhopedics, Faculty of Medicine, Juntendo University, Bunkyo-ku, Tokyo, Japan
| | - Mitsuaki Kubota
- Departments of Orhopedics, Faculty of Medicine, Juntendo University, Bunkyo-ku, Tokyo, Japan
| | - Muneaki Ishijima
- Departments of Orhopedics, Faculty of Medicine, Juntendo University, Bunkyo-ku, Tokyo, Japan
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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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19
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Shevela EY, Glebova TR, Kotova MA, Nitsa NA, Kozhevnikov YA, Meledina IV, Ostanin AA, Chernykh ER. Comparative Efficacy of the Stromal-Vascular Fraction Cells of Lipoaspirate and Hyaluronic Acid in the Treatment of Gonarthrosis: Results of an Interim Analysis. Bull Exp Biol Med 2022; 174:131-136. [PMID: 36437323 DOI: 10.1007/s10517-022-05661-6] [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: 02/21/2022] [Indexed: 11/29/2022]
Abstract
The use of cell technologies, in particular the stromal-vascular fraction of adipose tissue, is a new direction in the treatment of osteoarthritis of the weight-bearing joints. Stromal-vascular fraction cells have anti-inflammatory and immunomodulatory effects and are able to differentiate into connective tissue cells, including cartilage, tendons, and ligaments. Our clinical study showed the safety and good tolerability of intra-articular administration of autologous stromal-vascular fraction cells in 16 patients with severe manifestations of osteoarthritis. Single administration of stromal-vascular fraction cells led to more pronounced and stable (up to 12 months) clinical improvement in the main symptoms of the disease, including pain and functional activity of the affected joints, in comparison with intra-articular injection of hyaluronic acid (10 patients of the comparison group).
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Affiliation(s)
- E Ya Shevela
- Research Institute of Fundamental and Clinical Immunology, Novosibirsk, Russia.
| | - T R Glebova
- Research Institute of Fundamental and Clinical Immunology, Novosibirsk, Russia
| | - M A Kotova
- Research Institute of Fundamental and Clinical Immunology, Novosibirsk, Russia
| | - N A Nitsa
- Research Institute of Fundamental and Clinical Immunology, Novosibirsk, Russia
| | - Yu A Kozhevnikov
- Research Institute of Fundamental and Clinical Immunology, Novosibirsk, Russia
| | - I V Meledina
- Research Institute of Fundamental and Clinical Immunology, Novosibirsk, Russia
| | - A A Ostanin
- Research Institute of Fundamental and Clinical Immunology, Novosibirsk, Russia
| | - E R Chernykh
- Research Institute of Fundamental and Clinical Immunology, Novosibirsk, Russia
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20
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Tang Q, Zhao XS, Guo A, Cui RT, Song HL, Qi ZY, Pan Y, Yang Y, Zhang FF, Jin L. Therapeutic applications of adipose-derived stromal vascular fractions in osteoarthritis. World J Stem Cells 2022; 14:744-755. [PMID: 36337155 PMCID: PMC9630988 DOI: 10.4252/wjsc.v14.i10.744] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2022] [Revised: 07/08/2022] [Accepted: 09/12/2022] [Indexed: 02/07/2023] Open
Abstract
Osteoarthritis (OA) is considered to be a highly heterogeneous disease with progressive cartilage loss, subchondral bone remodeling, and low-grade inflammation. It is one of the world's leading causes of disability. Most conventional clinical treatments for OA are palliative drugs, which cannot fundamentally cure this disease. The stromal vascular fraction (SVF) from adipose tissues is a heterogeneous cell population. According to previous studies, it contains a large number of mesenchymal stem cells, which have been used to treat OA with good therapeutic results. This safe, simple, and effective therapy is expected to be applied and promoted in the future. In this paper, the detailed pathogenesis, diagnosis, and current clinical treatments for OA are introduced. Then, clinical studies and the therapeutic mechanism of SVF for the treatment of OA are summarized.
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Affiliation(s)
- Qi Tang
- School of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, Jiangsu Province, China
| | - Xian-Sheng Zhao
- Department of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, China
| | - Ao Guo
- School of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, Jiangsu Province, China
| | - Ruo-Tong Cui
- School of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, Jiangsu Province, China
| | - Huai-Le Song
- School of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, Jiangsu Province, China
| | - Zi-Yang Qi
- School of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, Jiangsu Province, China
| | - Yi Pan
- School of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, Jiangsu Province, China
| | - Yue Yang
- School of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, Jiangsu Province, China
| | - Fang-Fang Zhang
- School of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, Jiangsu Province, China
| | - Liang Jin
- School of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, Jiangsu Province, China
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21
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Schmitz C. Intra-articular Injections of Mesenchymal Stem Cells Without Adjuvant Therapies for Knee Osteoarthritis: A Systematic Review and Meta-analysis: Letter to the Editor. Am J Sports Med 2022; 50:NP48-NP49. [PMID: 36177754 DOI: 10.1177/03635465221112083] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
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22
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Rodriguez-Merchan EC. Autologous and Allogenic Utilization of Stromal Vascular Fraction and Decellularized Extracellular Matrices in Orthopedic Surgery: A Scoping Review. THE ARCHIVES OF BONE AND JOINT SURGERY 2022; 10:827-832. [PMID: 36452418 PMCID: PMC9702025 DOI: 10.22038/abjs.2022.59635.2943] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 08/11/2021] [Accepted: 03/05/2022] [Indexed: 01/25/2023]
Abstract
BACKGROUND This narrative review of the literature aims to analyze the utilization of stromal vascular fraction (SVF) and decellularized extracellular matrices (dECMs) in various pathologies related to orthopedic surgery. METHODS A literature search was carried out in PubMed on February 15, 2022, using "Stroma Vascular Fraction and Orthopedic Surgery" and "Decellularized Extracellular Matrices and Orthopedic Surgery" as keywords. A total of 278 articles were found, of which 28 papers were selected because they seemed to be the most appropriate concerning the title of the article. RESULTS The reported results have shown that intra-articular injection of SVF seems to be a safe and efficacious method for managing knee osteoarthritis (OA). Platelet-rich plasma (PRP) and SVF are safe and effective management for intractable Achilles tendinopathy in humans, although subjects treated with SVF recover earlier. There are promising results in utilizing adipose-derived mesenchymal stromal cells in chronic lateral epicondylitis of the elbow in athletes. Ready-to-use ECM/SVF gel seems to be a good therapeutic option promoting the regeneration of the articular cartilage in subjects with injuries of the cartilage. The SVF can safely be used to treat diabetic subjects suffering from chronic foot ulcers. CONCLUSION There are scarce high-quality data for utilizing cell-based approach in soft tissue injuries of the knee in athletes. Experimental studies indicate that SVF could be a new option to osseous regeneration. Other experimental studies support the utilization of dECMs as a scaffold for the regeneration of large osseous defects, cell-derived dECMs scaffolds to repair articular cartilage injuries, and utilization of xenogeneic acellular muscles to manage volumetric muscle loss where there is a lack of donor site.Intra-articular injections of SVF seems to be a safe and efficacious method for managing OA of the knee joint. Platelet-rich plasma (PRP) and SVF are safe and efficacious methods for the management of intractable Achilles tendinopathy in humans, although subjects treated with SVF recover earlier.
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23
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Lana JFSD, Lana AVSD, da Fonseca LF, Coelho MA, Marques GG, Mosaner T, Ribeiro LL, Azzini GOM, Santos GS, Fonseca E, de Andrade MAP. Stromal Vascular Fraction for Knee Osteoarthritis - An Update. J Stem Cells Regen Med 2022; 18:11-20. [PMID: 36003656 DOI: 10.46582/jsrm.1801003] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2021] [Accepted: 12/10/2021] [Indexed: 11/19/2022]
Abstract
Orthobiologics never cease to cause popularity within the medical science field, distinctly in regenerative medicine. Recently, adipose tissue has been an object of interest for many researchers and medical experts due to the fact that it represents a novel and potential cell source for tissue engineering and regenerative medicine purposes. Stromal vascular fraction (SVF), for instance, which is an adipose tissue-derivative, has generated optimistic results in many scenarios. Its biological potential can be harnessed and administered into injured tissues, particularly areas in which standard healing is disrupted. This is a typical feature of osteoarthritis (OA), a common degenerative joint disease which is outlined by persistent inflammation and destruction of surrounding tissues. SVF is known to carry a large amount of stem and progenitor cells, which are able to perform self-renewal, differentiation, and proliferation. Furthermore, they also secrete several cytokines and several growth factors, effectively sustaining immune modulatory effects and halting the escalated pro-inflammatory status of OA. Although SVF has shown interesting results throughout the medical community, additional research is still highly desirable in order to further elucidate its potential regarding musculoskeletal disorders, especially OA.
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Affiliation(s)
| | | | - Lucas Furtado da Fonseca
- Orthopaedic Department - Universidade Federal de São Paulo - Escola Paulista de Medicina, São Paulo - SP, Brazil
| | - Marcelo Amaral Coelho
- IOC - Instituto do Osso e da Cartilagem / The Bone and Cartilage Institute, Indaiatuba - SP, Brazil
| | | | - Tomas Mosaner
- IOC - Instituto do Osso e da Cartilagem / The Bone and Cartilage Institute, Indaiatuba - SP, Brazil
| | | | | | - Gabriel Silva Santos
- IOC - Instituto do Osso e da Cartilagem / The Bone and Cartilage Institute, Indaiatuba - SP, Brazil
| | - Eduardo Fonseca
- IOC - Instituto do Osso e da Cartilagem / The Bone and Cartilage Institute, Indaiatuba - SP, Brazil
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24
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Boada-Pladellorens A, Avellanet M, Pages-Bolibar E, Veiga A. Stromal vascular fraction therapy for knee osteoarthritis: a systematic review. Ther Adv Musculoskelet Dis 2022; 14:1759720X221117879. [PMID: 35991523 PMCID: PMC9386815 DOI: 10.1177/1759720x221117879] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Accepted: 07/19/2022] [Indexed: 12/17/2022] Open
Abstract
Background: Regenerative cell therapies, such as adipose-derived stromal vascular fraction (SVF), have been postulated as potential treatments for knee osteoarthritis (KOA). Objectives: To assess the efficacy and safety of SVF treatment against placebo and other standard therapies for treating KOA in adult patients. Design: A systematic review. Data sources and methods: We searched the following databases: MEDLINE via PubMed, Epistemonikos, PEDro, DynaMed, TripDatabase, Elsevier via Clinicalkey and Cochrane Controlled Trials Register. We included prospective interventional studies where treatment with SVF in adults with KOA was compared against placebo or other standard therapies, and results were objectively measured with at least one widely recognised osteoarthritis scale. Results: Among 266 studies published until May 2021, nine met our inclusion criteria. A total of 239 patients (274 knees) were included in our study. The follow-up ranged from 6 to 24 months. Six studies had a control group (only one being placebo). All studies showed that SVF improved pain and functionality measured, in most cases, with the visual analogue scale and the Western Ontario and McMaster Universities Osteoarthritis Index. In addition, five studies reported an improvement in anatomical structures, as detected in MR images. However, the number of cells contained in SVF varied substantially between different studies, which could induce a comparison bias. Conclusion: Although based on a small number of dissimilar studies, SVF was considered a safe treatment for KOA and could be promising in terms of pain, functionality and anatomical structure improvement. However, SVF products need to be standardised, the number of cells homogenised and the use of concomitant treatments reduced to establish proper comparisons. Registration: PROSPERO registration number: CRD42021284187.
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Affiliation(s)
- Anna Boada-Pladellorens
- Physical Medicine and Rehabilitation Department, Hospital Nostra Senyora de Meritxell, Carrer dels Escalls, AD700 Escaldes-Engordany, Andorra
| | - Mercè Avellanet
- Physical Medicine and Rehabilitation Department, Hospital Nostra Senyora de Meritxell, Escaldes-Engordany, Andorra
| | - Esther Pages-Bolibar
- Physical Medicine and Rehabilitation Department, Hospital Nostra Senyora de Meritxell, Escaldes-Engordany, Andorra
| | - Anna Veiga
- Barcelona Stem Cell Bank, Regenerative Medicine Programme, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Hospital Duran i Reynals, Barcelona, Spain
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25
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Frazier T, March K, Garza JR, Bunnell BA, Darr KF, Rogers E, Hamel K, Gimble JM. Non-homologous use of adipose-derived cell and tissue therapies: Osteoarthritis as a case study. Bone Rep 2022; 17:101601. [PMID: 35874168 PMCID: PMC9305321 DOI: 10.1016/j.bonr.2022.101601] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2022] [Revised: 06/22/2022] [Accepted: 06/29/2022] [Indexed: 01/09/2023] Open
Abstract
Adipose tissue is widely recognized as an abundant and accessible human tissue that serves as a source of cells and extracellular matrix scaffolds for regenerative surgical applications. Increasingly, orthopedic surgeons are turning to adipose tissue as a resource in their treatment of osteoarthritis and related conditions. In the U.S., the regulatory landscape governing the orthopedic surgical utilization of autologous and allogeneic adipose tissue remains complex. This manuscript reviews the Food and Drug Administration's nomenclature and guidance regarding adipose tissue products. Additionally, it surveys recent pre-clinical and clinical trial literature relating to the application of adipose-derived cells and tissues in the treatment of osteoarthritis.
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Affiliation(s)
- Trivia Frazier
- Obatala Sciences, New Orleans, LA, United States of America,Tulane University, New Orleans, LA, United States of America
| | - Keith March
- University of Florida, Gainesville, FL, United States of America
| | - Jaime R. Garza
- Tulane University, New Orleans, LA, United States of America,University of Texas Health Sciences Center - San Antonio, San Antonio, TX, United States of America
| | - Bruce A. Bunnell
- University of North Texas Health Science Center, Ft. Worth, TX, United States of America
| | - Kevin F. Darr
- Covington Orthopedics Sports Medicine Institute, Covington, LA, United States of America
| | - Emma Rogers
- Obatala Sciences, New Orleans, LA, United States of America
| | - Katie Hamel
- Obatala Sciences, New Orleans, LA, United States of America
| | - Jeffrey M. Gimble
- Obatala Sciences, New Orleans, LA, United States of America,Tulane University, New Orleans, LA, United States of America,Corresponding author at: Obatala Sciences, New Orleans, LA, United States of America.
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26
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Fujita M, Matsumoto T, Hayashi S, Hashimoto S, Nakano N, Maeda T, Kuroda Y, Takashima Y, Kikuchi K, Anjiki K, Ikuta K, Onoi Y, Tachibana S, Matsushita T, Iwaguro H, Sobajima S, Hiranaka T, Kuroda R. Paracrine effect of the stromal vascular fraction containing M2 macrophages on human chondrocytes through the Smad2/3 signaling pathway. J Cell Physiol 2022; 237:3627-3639. [PMID: 35766589 DOI: 10.1002/jcp.30823] [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: 07/20/2021] [Revised: 05/27/2022] [Accepted: 06/17/2022] [Indexed: 11/08/2022]
Abstract
The adipose-derived stromal vascular fraction (SVF) is composed of a heterogeneous mix of adipose-derived stem cells (ADSCs), macrophages, pericytes, fibroblasts, blood, and other cells. Previous studies have found that the paracrine effects of SVF cells may be therapeutic, but their role in osteoarthritis treatment remains unclear. This study aimed to investigate the therapeutic effect of SVF cells on chondrocytes. Chondrocytes were seeded on culture plates alone (control) or cocultured with SVF or ADSCs on cell culture inserts. After 48 h of coculture, chondrocyte collagen II, tissue inhibitors of metalloproteinases-3 (TIMP-3), and matrix metalloproteinases-13 (MMP-13) messenger RNA (mRNA) expression levels were evaluated using reverse-transcription polymerase chain reaction, and the transforming growth factor-β (TGF-β) levels in the supernatant were measured using ELISA. Immunohistochemical staining and flow cytometry were used to evaluate the macrophages in the SVF. These macrophages were characterized according to phenotype using the F4/80, CD86, and CD163 markers. To determine whether the Smad2/3 signaling pathways were involved, the chondrocytes were pre-treated with a Smad2/3 phosphorylation inhibitor and stimulated with the SVF, and then Smad2/3 phosphorylation levels were analyzed using western blot. The mRNA expression levels of various paracrine factors and chondrocyte pellet size were also assessed. Collagen II and TIMP-3 expression were higher in the SVF group than in the ADSC group and controls, while MMP-13 expression was the highest in the ADSC group and the lowest in the controls. TGF-β levels in the SVF group were also elevated. Immunohistochemical staining and flow cytometry revealed that the macrophages in the SVF were of the anti-inflammatory phenotype. Western blot analysis showed that the SVF increased Smad2/3 phosphorylation, while Smad2/3 inhibitors decreased phosphorylation. Smad2/3 inhibitors also reduced the expression of various other paracrine factors and decreased chondrocyte pellet size. These findings suggested that the paracrine effect of heterogeneous cells, such as anti-inflammatory macrophages, in the SVF partly supports chondrocyte regeneration through TGF-β-induced Smad2/3 phosphorylation.
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Affiliation(s)
- Masahiro Fujita
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Tomoyuki Matsumoto
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Shinya Hayashi
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Shingo Hashimoto
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Naoki Nakano
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Toshihisa Maeda
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Yuichi Kuroda
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Yoshinori Takashima
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Kenichi Kikuchi
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Kensuke Anjiki
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Kemmei Ikuta
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Yuma Onoi
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Shotaro Tachibana
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Takehiko Matsushita
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Hideki Iwaguro
- Department of Orthopaedic Surgery, Sobajima Clinic, Osaka, Japan
| | - Satoshi Sobajima
- Department of Orthopaedic Surgery, Sobajima Clinic, Osaka, Japan
| | - Takafumi Hiranaka
- Department of Orthopaedic Surgery and Joint Surgery Centre, Takatsuki General Hospital, Osaka, Japan
| | - Ryosuke Kuroda
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
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27
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Bolia IK, Bougioukli S, Hill WJ, Trasolini NA, Petrigliano FA, Lieberman JR, Weber AE. Clinical Efficacy of Bone Marrow Aspirate Concentrate Versus Stromal Vascular Fraction Injection in Patients With Knee Osteoarthritis: A Systematic Review and Meta-analysis. Am J Sports Med 2022; 50:1451-1461. [PMID: 34102078 DOI: 10.1177/03635465211014500] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND Knee injection using either bone marrow aspirate concentrate (BMAC) or stromal vascular fraction (SVF) from adipose tissue has been shown to result in symptomatic improvement in patients with knee osteoarthritis (OA). It is still unclear whether one of these therapies is superior over the other. PURPOSE To systematically report the clinical studies evaluating BMAC and SVF in the treatment of knee OA and to compare the clinical efficacy of these 2 injection therapies. STUDY DESIGN Meta-analysis; Level of evidence, 4. METHODS This meta-analysis was performed per the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines. Studies were included if they reported the clinical outcomes after a single BMAC or SVF injection in the knee joint of patients with OA. Studies evaluating preparations of culture-expanded stem cells were excluded. A random effects model was used; the clinical efficacy of BMAC or SVF injection was assessed using the standardized mean difference (SMD) and compared. Visual analog scale (VAS) scores for pain and Western Ontario and McMaster Universities Osteoarthritis (WOMAC) knee index were the primary outcomes. The level of statistical significance was set at P < .05. RESULTS Ten studies and 472 patients with knee OA who received either BMAC (233 patients) or SVF (239 patients) were included. Patients who received an injection had improved VAS outcomes (mean ± SD): from 5.8 ± 1.3 to 2.6 ± 17 for BMAC and from 6.4 ± 1.4 to 3.4 ± 0.5 for SVF. They also experienced significantly reduced pain (SMD [VAS], 2.6 for BMAC and 3.4 for SVF) and improved function (SMD [WOMAC], 1.4 for BMAC and 1.2 for SVF). However, the SVF injection had a significantly greater effect on pain reduction than did the BMAC injection (P < .0001). Based on WOMAC, the clinical effect of BMAC versus SVF knee injection in patients with knee OA was equivalent (P = .626). Results were limited by the presence of publication bias as well as variability in the preparation methods utilized in the BMAC and SVF injection protocols. Complications were reported in 50% of the BMAC studies (knee stiffness, persistent knee swelling) and 67% of the SVF studies (knee swelling, knee pain, positive SVF cultures without symptoms of infection, and bleeding at the abdominal harvest site). CONCLUSION A single BMAC or SVF injection into the knee joint of patients with OA resulted in symptomatic improvement at short-term follow-up. However, SVF seemed to be more effective than did BMAC in the reduction of knee pain. There was significant variation in the BMAC and SVF injection preparation techniques used across the studies and a lack of stratification of outcomes based on the radiologic classification of OA. Therefore, these results should be taken with caution.
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Affiliation(s)
- Ioanna K Bolia
- USC Epstein Family Center for Sports Medicine at Keck Medicine of USC, Los Angeles, California, USA
| | - Sofia Bougioukli
- USC Epstein Family Center for Sports Medicine at Keck Medicine of USC, Los Angeles, California, USA
| | - William J Hill
- USC Epstein Family Center for Sports Medicine at Keck Medicine of USC, Los Angeles, California, USA
| | - Nicholas A Trasolini
- USC Epstein Family Center for Sports Medicine at Keck Medicine of USC, Los Angeles, California, USA
| | - Frank A Petrigliano
- USC Epstein Family Center for Sports Medicine at Keck Medicine of USC, Los Angeles, California, USA
| | - Jay R Lieberman
- USC Epstein Family Center for Sports Medicine at Keck Medicine of USC, Los Angeles, California, USA
| | - Alexander E Weber
- USC Epstein Family Center for Sports Medicine at Keck Medicine of USC, Los Angeles, California, USA
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28
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Methodological Flaws in Meta-Analyses of Clinical Studies on the Management of Knee Osteoarthritis with Stem Cells: A Systematic Review. Cells 2022; 11:cells11060965. [PMID: 35326416 PMCID: PMC8946093 DOI: 10.3390/cells11060965] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Revised: 03/08/2022] [Accepted: 03/09/2022] [Indexed: 12/13/2022] Open
Abstract
(1) Background: Conclusions of meta-analyses of clinical studies may substantially influence opinions of prospective patients and stakeholders in healthcare. Nineteen meta-analyses of clinical studies on the management of primary knee osteoarthritis (pkOA) with stem cells, published between January 2020 and July 2021, came to inconsistent conclusions regarding the efficacy of this treatment modality. It is possible that a separate meta-analysis based on an independent, systematic assessment of clinical studies on the management of pkOA with stem cells may reach a different conclusion. (2) Methods: PubMed, Web of Science, and the Cochrane Library were systematically searched for clinical studies and meta-analyses of clinical studies on the management of pkOA with stem cells. All clinical studies and meta-analyses identified were evaluated in detail, as were all sub-analyses included in the meta-analyses. (3) Results: The inconsistent conclusions regarding the efficacy of treating pkOA with stem cells in the 19 assessed meta-analyses were most probably based on substantial differences in literature search strategies among different authors, misconceptions about meta-analyses themselves, and misconceptions about the comparability of different types of stem cells with regard to their safety and regenerative potential. An independent, systematic review of the literature yielded a total of 183 studies, of which 33 were randomized clinical trials, including a total of 6860 patients with pkOA. However, it was not possible to perform a scientifically sound meta-analysis. (4) Conclusions: Clinicians should interpret the results of the 19 assessed meta-analyses of clinical studies on the management of pkOA with stem cells with caution and should be cautious of the conclusions drawn therein. Clinicians and researchers should strive to participate in FDA and/or EMA reviewed and approved clinical trials to provide clinically and statistically valid efficacy.
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29
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Labarre KW, Zimmermann G. Infiltration of the Hoffa's fat pad in patients with osteoarthritis of the knee-Results after one year of follow-up. Bone Rep 2022; 16:101168. [PMID: 35733948 PMCID: PMC9207720 DOI: 10.1016/j.bonr.2022.101168] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Revised: 01/12/2022] [Accepted: 01/18/2022] [Indexed: 12/15/2022] Open
Abstract
Objectives Cell therapy using multipotential stromal cells (MSCs) is being used in a variety of clinical settings to induce tissue regeneration. Promising results have also been achieved in the therapy of osteoarthritis. MSCs have been demonstrated to be safe (Borakati et al., 2018). They can be used in a one step procedure as minimally manipulated mesenchymal stem cells or after in vitro expansion. The in vitro step allows for the selection of a more homogeneous cell population, meeting the standard criteria for MSC identification (Lv et al., 2014). In vitro expansion of MSCs is cost intensive, time consuming and furthermore associated with gradual accumulation of senescent cells (Wagner et al., 2008), telomere erosion (Baxter et al., 2004), and changing phenotypes (Jones et al., 2010; Halfon et al., 2011). These disadvantages could be surpassed by the use of “minimally manipulated mesenchymal stem cells” from bone marrow or adipose tissue (Di Matteo et al., 2019) such as the adipogenic stromal-vascular fraction (SVF). The study investigates whether infiltration of the Hoffa fat pad with autologous SVF is an effective and safe treatment option for patients with gonarthrosis. Furthermore, the number and vitality of the injected cells as well as the clinical efficacy will be evaluated. Materials and methods We conduct a prospective study. Patients with osteoarthritis of the knee receive infiltration of SVF into the Hoffa fat pad. The number and vitality of the cells are measured with a cell counter. The clinical outcome is checked using VAS, KOOS and SF12 questionnaires with a follow-up period of 1 year. Results A total of 33 patients and 36 knees were included in this Study. An average of 45 million cells were injected with a standard deviation of 2,5 million Cells. After 6 months a significant improvement of the VAS and the respective subscales of the KOOS could be observed compared to the baseline. After one year of follow-up, a significant improvement in all KOOS subscales compared to baseline was still observed. A significant correlation between reduced knee pain on the VAS and the number of injected cells could be observed as well. Thus, patients injected with a higher number of cells seem to have a better outcome. The average viability of the cells was 64,4% with a standard deviation of 15,9%. A correlation between higher cell viability and better outcome on the QOL subscale of the KOOS was observed. There were no major complications or side effects. Discussion These initial results indicate that treatment with SVF is a safe therapeutic option that has the potential to relieve joint pain and significantly improved function. The cell number and vitality of the injected cells appear to be important factors influencing the success of the therapy.
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Peláez P, Damiá E, Torres-Torrillas M, Chicharro D, Cuervo B, Miguel L, del Romero A, Carrillo JM, Sopena JJ, Rubio M. Cell and Cell Free Therapies in Osteoarthritis. Biomedicines 2021; 9:1726. [PMID: 34829953 PMCID: PMC8615373 DOI: 10.3390/biomedicines9111726] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Revised: 11/12/2021] [Accepted: 11/16/2021] [Indexed: 12/18/2022] Open
Abstract
Osteoarthritis (OA) is the most common articular disease in adults and has a current prevalence of 12% in the population over 65 years old. This chronic disease causes damage to articular cartilage and synovial joints, causing pain and leading to a negative impact on patients' function, decreasing quality of life. There are many limitations regarding OA conventional therapies-pharmacological therapy can cause gastrointestinal, renal, and cardiac adverse effects, and some of them could even be a threat to life. On the other hand, surgical options, such as microfracture, have been used for the last 20 years, but hyaline cartilage has a limited regeneration capacity. In recent years, the interest in new therapies, such as cell-based and cell-free therapies, has been considerably increasing. The purpose of this review is to describe and compare bioregenerative therapies' efficacy for OA, with particular emphasis on the use of mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP). In OA, these therapies might be an alternative and less invasive treatment than surgery, and a more effective option than conventional therapies.
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Affiliation(s)
- Pau Peláez
- Bioregenerative Medicine and Applied Surgery Research Group, Department of Animal Medicine and Surgery, CEU Cardenal Herrera University, CEU Universities, C/Tirant lo Blanc, 7, Alfara del Patriarca, 46115 Valencia, Spain; (P.P.); (M.T.-T.); (D.C.); (B.C.); (L.M.); (A.d.R.); (J.M.C.); (J.J.S.); (M.R.)
- Garcia Cugat Foundation CEU-UCH Chair of Medicine and Regenerative Surgery, 08006 Barcelona, Spain
| | - Elena Damiá
- Bioregenerative Medicine and Applied Surgery Research Group, Department of Animal Medicine and Surgery, CEU Cardenal Herrera University, CEU Universities, C/Tirant lo Blanc, 7, Alfara del Patriarca, 46115 Valencia, Spain; (P.P.); (M.T.-T.); (D.C.); (B.C.); (L.M.); (A.d.R.); (J.M.C.); (J.J.S.); (M.R.)
- Garcia Cugat Foundation CEU-UCH Chair of Medicine and Regenerative Surgery, 08006 Barcelona, Spain
| | - Marta Torres-Torrillas
- Bioregenerative Medicine and Applied Surgery Research Group, Department of Animal Medicine and Surgery, CEU Cardenal Herrera University, CEU Universities, C/Tirant lo Blanc, 7, Alfara del Patriarca, 46115 Valencia, Spain; (P.P.); (M.T.-T.); (D.C.); (B.C.); (L.M.); (A.d.R.); (J.M.C.); (J.J.S.); (M.R.)
- Garcia Cugat Foundation CEU-UCH Chair of Medicine and Regenerative Surgery, 08006 Barcelona, Spain
| | - Deborah Chicharro
- Bioregenerative Medicine and Applied Surgery Research Group, Department of Animal Medicine and Surgery, CEU Cardenal Herrera University, CEU Universities, C/Tirant lo Blanc, 7, Alfara del Patriarca, 46115 Valencia, Spain; (P.P.); (M.T.-T.); (D.C.); (B.C.); (L.M.); (A.d.R.); (J.M.C.); (J.J.S.); (M.R.)
- Garcia Cugat Foundation CEU-UCH Chair of Medicine and Regenerative Surgery, 08006 Barcelona, Spain
| | - Belén Cuervo
- Bioregenerative Medicine and Applied Surgery Research Group, Department of Animal Medicine and Surgery, CEU Cardenal Herrera University, CEU Universities, C/Tirant lo Blanc, 7, Alfara del Patriarca, 46115 Valencia, Spain; (P.P.); (M.T.-T.); (D.C.); (B.C.); (L.M.); (A.d.R.); (J.M.C.); (J.J.S.); (M.R.)
- Garcia Cugat Foundation CEU-UCH Chair of Medicine and Regenerative Surgery, 08006 Barcelona, Spain
| | - Laura Miguel
- Bioregenerative Medicine and Applied Surgery Research Group, Department of Animal Medicine and Surgery, CEU Cardenal Herrera University, CEU Universities, C/Tirant lo Blanc, 7, Alfara del Patriarca, 46115 Valencia, Spain; (P.P.); (M.T.-T.); (D.C.); (B.C.); (L.M.); (A.d.R.); (J.M.C.); (J.J.S.); (M.R.)
- Garcia Cugat Foundation CEU-UCH Chair of Medicine and Regenerative Surgery, 08006 Barcelona, Spain
| | - Ayla del Romero
- Bioregenerative Medicine and Applied Surgery Research Group, Department of Animal Medicine and Surgery, CEU Cardenal Herrera University, CEU Universities, C/Tirant lo Blanc, 7, Alfara del Patriarca, 46115 Valencia, Spain; (P.P.); (M.T.-T.); (D.C.); (B.C.); (L.M.); (A.d.R.); (J.M.C.); (J.J.S.); (M.R.)
- Garcia Cugat Foundation CEU-UCH Chair of Medicine and Regenerative Surgery, 08006 Barcelona, Spain
| | - Jose Maria Carrillo
- Bioregenerative Medicine and Applied Surgery Research Group, Department of Animal Medicine and Surgery, CEU Cardenal Herrera University, CEU Universities, C/Tirant lo Blanc, 7, Alfara del Patriarca, 46115 Valencia, Spain; (P.P.); (M.T.-T.); (D.C.); (B.C.); (L.M.); (A.d.R.); (J.M.C.); (J.J.S.); (M.R.)
- Garcia Cugat Foundation CEU-UCH Chair of Medicine and Regenerative Surgery, 08006 Barcelona, Spain
| | - Joaquín J. Sopena
- Bioregenerative Medicine and Applied Surgery Research Group, Department of Animal Medicine and Surgery, CEU Cardenal Herrera University, CEU Universities, C/Tirant lo Blanc, 7, Alfara del Patriarca, 46115 Valencia, Spain; (P.P.); (M.T.-T.); (D.C.); (B.C.); (L.M.); (A.d.R.); (J.M.C.); (J.J.S.); (M.R.)
- Garcia Cugat Foundation CEU-UCH Chair of Medicine and Regenerative Surgery, 08006 Barcelona, Spain
| | - Mónica Rubio
- Bioregenerative Medicine and Applied Surgery Research Group, Department of Animal Medicine and Surgery, CEU Cardenal Herrera University, CEU Universities, C/Tirant lo Blanc, 7, Alfara del Patriarca, 46115 Valencia, Spain; (P.P.); (M.T.-T.); (D.C.); (B.C.); (L.M.); (A.d.R.); (J.M.C.); (J.J.S.); (M.R.)
- Garcia Cugat Foundation CEU-UCH Chair of Medicine and Regenerative Surgery, 08006 Barcelona, Spain
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Attenuation of Knee Osteoarthritis Progression in Mice through Polarization of M2 Macrophages by Intra-Articular Transplantation of Non-Cultured Human Adipose-Derived Regenerative Cells. J Clin Med 2021; 10:jcm10194309. [PMID: 34640324 PMCID: PMC8509129 DOI: 10.3390/jcm10194309] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2021] [Revised: 09/16/2021] [Accepted: 09/17/2021] [Indexed: 12/12/2022] Open
Abstract
Adipose-derived regenerative cells (ADRCs) are non-cultured heterogeneous or mixed populations of cells obtained from adipose tissue by collagenase digestion. The injection of ADRCs have been tried clinically for the treatment of osteoarthritis (OA). The purpose of this study was to evaluate the effect of intra-articular transplantation of human ADRCs on OA progression in mice and the effect of ADRCs on macrophage polarization. In in vivo experiments, BALB/c-nu mice with knee OA received intra-articular transplantation of either phosphate buffered-saline or human ADRCs. OA progression was evaluated histologically and significantly attenuated in the ADRC group at both four and eight weeks postoperatively. The expression of OA-related proteins in the cartilage and macrophage-associated markers in the synovium were examined by immunohistochemistry. The numbers of MMP-13-, ADAMTS-5-, IL-1β-, IL-6- and iNOS-positive cells significantly decreased, and type II collagen- and CD206-positive cells were more frequently detected in the ADRC group compared with that in the control group. In vitro co-culture experiments showed that ADRCs induced macrophage polarization toward M2. The results of this study suggest that the intra-articular transplantation of human ADRCs could attenuate OA progression possibly by reducing catabolic factors in chondrocytes and modulating macrophage polarization.
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Tan SHS, Kwan YT, Neo WJ, Chong JY, Kuek TYJ, See JZF, Wong KL, Toh WS, Hui JHP. Intra-articular Injections of Mesenchymal Stem Cells Without Adjuvant Therapies for Knee Osteoarthritis: A Systematic Review and Meta-analysis. Am J Sports Med 2021; 49:3113-3124. [PMID: 33471552 DOI: 10.1177/0363546520981704] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND While many reviews have been performed to attempt to provide conclusive evidence regarding the outcomes of mesenchymal stem cells (MSCs) in osteoarthritis treatment, the evidence for MSC treatment in osteoarthritis remains contentious, as these reviews have been limited by the heterogeneous evidence available. PURPOSE To pool the results of treatment using intra-articular injections of MSCs without any adjuvant therapies for osteoarthritis. STUDY DESIGN Systematic review and meta-analysis. METHODS The review was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. All clinical trials of level 1 or 2 evidence that reported clinical outcomes of patients with osteoarthritis of the knees treated using intra-articular injections of MSCs without any adjuvant therapies were included. RESULTS A total of 19 studies with 440 knees were included. All studies reported an improvement in the outcomes after intervention. The standardized mean differences (SMDs) for the visual analog scale (VAS) for pain at rest and upon exertion were -1.48 (95% CI, -1.85 to -1.11) and -2.25 (95% CI, -2.64 to -1.85), respectively. The SMDs for the total Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and total Knee injury and Osteoarthritis Outcome Score were -1.19 (95% CI, -1.53 to -0.84) and 0.88 (95% CI, 0.66-1.10), respectively. Only the source of MSCs and whether the MSCs were cultured or uncultured were clinically important and statistically significant moderators of the treatment outcome. The use of bone marrow MSCs reduced the VAS for pain by 1.50 (95% CI, 0.04-2.96; P = .04) and reduced the total WOMAC by 23.2 (95% CI, 10.0-36.4; P < .01) as compared with adipose MSCs. The use of cultured MSCs reduced the VAS for pain by 2.19 (95% CI, 0.57-3.81; P < .01) and reduced the total WOMAC by 14.4 (95% CI, 1.21-27.5; P = .03) as compared with uncultured MSCs. CONCLUSION Intra-articular injections of MSCs without any adjuvant therapies improves pain and function for osteoarthritis. Significantly better outcomes were obtained with the use of bone marrow MSCs as compared with adipose MSCs and with the use of cultured MSCs as opposed to uncultured MSCs.
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Affiliation(s)
- Si Heng Sharon Tan
- Department of Orthopaedic Surgery, National University Health System, Singapore
| | - Yiu Tsun Kwan
- Department of Orthopaedic Surgery, National University Health System, Singapore
| | - Wei Jian Neo
- Department of Orthopaedic Surgery, National University Health System, Singapore
| | - Jia Yan Chong
- Department of Orthopaedic Surgery, National University Health System, Singapore
| | - Tze Yin Joshua Kuek
- Department of Orthopaedic Surgery, National University Health System, Singapore
| | - Jun Ze Fabian See
- Department of Orthopaedic Surgery, National University Health System, Singapore
| | - Keng Lin Wong
- Department of Orthopaedic Surgery, National University Health System, Singapore.,Department of Orthopaedic Surgery, Sengkang General Hospital, Singapore
| | - Wei Seong Toh
- Tissue Engineering Program, Life Sciences Institute, National University of Singapore, Singapore.,Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore
| | - James Hoi Po Hui
- Department of Orthopaedic Surgery, National University Health System, Singapore.,Tissue Engineering Program, Life Sciences Institute, National University of Singapore, Singapore
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Kon E, Di Matteo B. Editorial Commentary: Minimally Invasive Strategies for Osteoarthritis: From Platelets to Mesenchymal Stem Cells. Arthroscopy 2021; 37:2258-2261. [PMID: 34226012 DOI: 10.1016/j.arthro.2021.04.010] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2021] [Accepted: 04/07/2021] [Indexed: 02/02/2023]
Abstract
The range of biological agents to treat osteoarthritis is in constant expansion, and recent trials suggest that amnion-derived products (such as umbilical cord stem cells or amniotic allograft suspension) may provide significant symptomatic relief and functional improvement compared with traditional injectables. Anyway, in many countries, stringent limitations exist on the manipulation and homologous use of placenta-derived products, and therefore, collecting more data is mandatory to endorse their use for musculoskeletal diseases in a safe and clearly regulated way. More in general, an increasing interest toward orthobiology has been observed in recent years, which led to the introduction in clinical practice of many minimally invasive strategies to treat osteoarthritis, from platelet-rich plasma to mesenchymal stem cells. On the basis of this trend, which involves physicians from different specialties, it would be fundamental to have clear guidelines establishing the correct use of these products in the setting of clinical routine not only to safely provide patients the most advanced therapeutic options but also to protect our practice from potential legal issues.
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Affiliation(s)
- Elizaveta Kon
- Humanitas University (E.K., B.D.M.); IRCCS Humanitas Research Hospital (E.K., B.D.M.); Sechenov - First Moscow State Medical University (E.K., B.D.M.)
| | - Berardo Di Matteo
- Humanitas University (E.K., B.D.M.); IRCCS Humanitas Research Hospital (E.K., B.D.M.); Sechenov - First Moscow State Medical University (E.K., B.D.M.)
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Natali S, Screpis D, Farinelli L, Iacono V, Vacca V, Gigante A, Zorzi C. The use of intra-articular injection of autologous micro-fragmented adipose tissue as pain treatment for ankle osteoarthritis: a prospective not randomized clinical study. INTERNATIONAL ORTHOPAEDICS 2021; 45:2239-2244. [PMID: 34142184 DOI: 10.1007/s00264-021-05093-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/07/2021] [Accepted: 05/24/2021] [Indexed: 01/16/2023]
Abstract
PURPOSE The objective of this study was to evaluate the safety and the efficacy of intra-articular injections of autologous micro-fragmented adipose tissue in patients affected by early or moderate ankle osteoarthritis (AOA). METHODS A total of 31 symptomatic patients, aged 28-71 years, affected by AOA, were treated with 5 ml of autologous micro-fragmented adipose tissue. Clinical evaluations before the treatment and after six, 12, and 24 months were performed through American Orthopaedic Foot and Ankle Society (AOFAS) scale, the Foot and Ankle Disability Index (FADI), and Visual Analogue Scale (VAS) scores. Adverse events were recorded. RESULTS No severe complications were noted during the treatment and the follow-up period. A statistically significant improvement from basal evaluation to the six, 12-, and 24-month follow-up visit was observed, whereas a statistically significant worsening from the 12-month to the 24-month follow-up visit was showed. CONCLUSION The autologous micro-fragmented adipose tissue for the treatment of pain in ankle osteoarthritis seems safe and able to provide positive clinical outcomes, potentially offering a new minimally invasive therapeutic option for patients who are not eligible for more invasive approaches. Further high-quality studies are needed to confirm these findings.
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Affiliation(s)
- Simone Natali
- Department of Orthopaedics, IRCCS Ospedale Sacro Cuore Don Calabria, Negrar di Valpolicella, Italy.
| | - Daniele Screpis
- Department of Orthopaedics, IRCCS Ospedale Sacro Cuore Don Calabria, Negrar di Valpolicella, Italy
| | - Luca Farinelli
- Clinical Ortopaedics, Department of Clinical and Molecular Sciences, Università Politecnica Delle Marche, Ancona, Italy
| | - Venanzio Iacono
- Department of Orthopaedics, IRCCS Ospedale Sacro Cuore Don Calabria, Negrar di Valpolicella, Italy
| | - Vittorio Vacca
- Department of Orthopaedics, IRCCS Ospedale Sacro Cuore Don Calabria, Negrar di Valpolicella, Italy
| | - Antonio Gigante
- Clinical Ortopaedics, Department of Clinical and Molecular Sciences, Università Politecnica Delle Marche, Ancona, Italy
| | - Claudio Zorzi
- Department of Orthopaedics, IRCCS Ospedale Sacro Cuore Don Calabria, Negrar di Valpolicella, Italy
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Kamenaga T, Kuroda Y, Nagai K, Tsubosaka M, Takashima Y, Kikuchi K, Fujita M, Ikuta K, Anjiki K, Maeda T, Nakano N, Takayama K, Hashimoto S, Hayashi S, Matsushita T, Niikura T, Kuroda R, Matsumoto T. Cryopreserved human adipose-derived stromal vascular fraction maintains fracture healing potential via angiogenesis and osteogenesis in an immunodeficient rat model. Stem Cell Res Ther 2021; 12:110. [PMID: 33541427 PMCID: PMC7863470 DOI: 10.1186/s13287-021-02182-3] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2020] [Accepted: 01/24/2021] [Indexed: 12/20/2022] Open
Abstract
Background Novel therapeutic strategies for the healing of nonunion, which has serious effects on the quality of life of patients, are needed. We evaluated the therapeutic effect of local transplantation of human stromal vascular fraction (SVF) cells on fracture healing in a rat non-healing fracture model and compared the effects between freshly isolated (F) and cryopreserved (C)-SVFs. Methods Non-healing fracture model was induced in the femur of female immunodeficient rats (F344/N Jcl rnu/rnu) with cauterizing periosteum. Immediately after the creation of non-healing fracture, rats received local transplantation of F and C-SVFs suspended in phosphate-buffered saline (PBS) or the same volume of PBS without cells using the same scaffold as a control group. During 8 weeks post-surgery, radiologic, histological, immunohistochemical, and biomechanical analyses were performed to evaluate fracture healing. The comparison of radiological results was performed with a chi-square test, and the multiple comparisons of immunohistochemical, histological, and biomechanical results among groups were made using a one-way analysis of variance. A probability value of 0.05 was considered to denote statistical significance. Results At week 8, in 60% of animals receiving F-SVF cells and in 50% of animals receiving C-SVF cells, the fracture radiologically healed with bone union whereas nonunion was observed in the control group. The healing potential was also confirmed by histological and biomechanical assessments. One of the mechanisms underlying healing involving intrinsic angiogenesis/osteogenesis was enhanced in F- and C-SVF groups compared with that in the control group. Human cell-derived vasculogenesis/osteogenesis, which was also confirmed in an in vitro differentiation assay, was also enhanced in the F- and C-SVF groups compared with that in the control groups and could be another mechanism for healing. Conclusions SVF cells can enhance bone healing and cryopreserved cells have almost equal potential as fresh cells. SVF cells can be used for improving nonunion bone fracture healing as an alternative to other mesenchymal stem cells and the effect of SVF cells can be maintained under cryopreservation.
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Affiliation(s)
- Tomoyuki Kamenaga
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-chou, 650-0017, Kobe, Japan
| | - Yuichi Kuroda
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-chou, 650-0017, Kobe, Japan
| | - Kanto Nagai
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-chou, 650-0017, Kobe, Japan
| | - Masanori Tsubosaka
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-chou, 650-0017, Kobe, Japan
| | - Yoshinori Takashima
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-chou, 650-0017, Kobe, Japan
| | - Kenichi Kikuchi
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-chou, 650-0017, Kobe, Japan
| | - Masahiro Fujita
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-chou, 650-0017, Kobe, Japan
| | - Kemmei Ikuta
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-chou, 650-0017, Kobe, Japan
| | - Kensuke Anjiki
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-chou, 650-0017, Kobe, Japan
| | - Toshihisa Maeda
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-chou, 650-0017, Kobe, Japan
| | - Naoki Nakano
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-chou, 650-0017, Kobe, Japan
| | - Koji Takayama
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-chou, 650-0017, Kobe, Japan
| | - Shingo Hashimoto
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-chou, 650-0017, Kobe, Japan
| | - Shinya Hayashi
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-chou, 650-0017, Kobe, Japan
| | - Takehiko Matsushita
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-chou, 650-0017, Kobe, Japan
| | - Takahiro Niikura
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-chou, 650-0017, Kobe, Japan
| | - Ryosuke Kuroda
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-chou, 650-0017, Kobe, Japan
| | - Tomoyuki Matsumoto
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-chou, 650-0017, Kobe, Japan.
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Shanmugasundaram S, Vaish A, Chavada V, Murrell WD, Vaishya R. Assessment of safety and efficacy of intra-articular injection of stromal vascular fraction for the treatment of knee osteoarthritis-a systematic review. INTERNATIONAL ORTHOPAEDICS 2021; 45:615-625. [PMID: 33432400 DOI: 10.1007/s00264-020-04926-x] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/04/2020] [Accepted: 12/29/2020] [Indexed: 12/19/2022]
Abstract
PURPOSE Stromal vascular fraction (SVF) as an injectable regenerative therapy for knee osteoarthritis (OA) has gained recent popularity. However, there is no clear consensus on the outcomes of such treatment. We systematically reviewed available evidence on the use of SVF injection in the treatment of knee OA. METHODS The study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, with keyword search in PubMed, Scopus, and the Cochrane Library Database and related article search in Google Scholar. Clinical studies demonstrating effects of SVF in knee OA and published in English literature were included. Risk of bias assessment was done with modified Coleman Methodology Scoring (CMS). RESULTS Eleven studies (9 prospective, 2 retrospective) that contributed to 290 knees in 200 patients were included. Two studies that contributed to 3718 knee injections were excluded from pooled analysis and were scrutinized separately. Majority of patients reported improvement in pain, range of motion (ROM), functional rating, six metre walking distance, and functional outcome scores. There was no major donor-site morbidity. There was only one reported case of knee joint infection and no case of tumour formation in relation to SVF injection. DISCUSSION Intra-articular injection of SVF can be a simple, affordable, and minimally invasive treatment that could serve as an interim option for patients who failed other conservative and arthroscopic options. CONCLUSION Intra-articular injection of SVF is a safe and effective technique for the management of knee OA. However, comparative Level I studies are needed to support the use of adjuvants with SVF and also to compare the use of SVF (with or without adjuvants) with ADMSCs, PRP, and bone marrow concentrate.
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Affiliation(s)
| | - Abhishek Vaish
- Department of Orthopedics, Indraprastha Apollo Hospitals, New Delhi, India
| | - Vijay Chavada
- Department of Community Medicine, Indira Gandhi Medical College and Research Institute, Pondicherry, India
| | - William D Murrell
- Abu Dhabi Knee and Sports Medicine, Healthpoint Hospital, Abu Dhabi, United Arab Emirates.,Department of Orthopaedic Surgery, William Beaumont Army Medical Center, Fort Bliss, El Paso, TX, USA
| | - Raju Vaishya
- Department of Orthopaedics, Indraprastha Apollo Hospital, New Delhi, India
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Tsubosaka M, Matsumoto T, Sobajima S, Matsushita T, Iwaguro H, Kuroda R. Comparison of Clinical and Imaging Outcomes of Different Doses of Adipose-Derived Stromal Vascular Fraction Cell Treatment for Knee Osteoarthritis. Cell Transplant 2021; 30:9636897211067454. [PMID: 35392685 PMCID: PMC9003644 DOI: 10.1177/09636897211067454] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2021] [Revised: 11/21/2021] [Accepted: 12/01/2021] [Indexed: 12/14/2022] Open
Abstract
Favorable clinical outcomes of intra-articular injection of adipose-derived stromal vascular fraction (SVF) cells for knee osteoarthritis (OA) have been reported, but the effects of different doses of SVF cells have not been examined. This study aimed to compare the short-term clinical and imaging outcomes of different doses of SVF cells for knee OA treatment. This study included 60 patients with knee OA who underwent intra-articular injection of SVF cells. The follow-up period was at least 12 months. Thirty patients received an intra-articular injection of 2.5×107 SVF cells (low-dose group), and the remaining 30 patients received an intra-articular injection of 5.0×107 SVF cells (high-dose group). Clinical evaluations were performed for the Knee injury and Osteoarthritis Outcome Score (KOOS). Imaging evaluations, including the magnetic resonance imaging Osteoarthritis Knee Score (MOAKS) features (bone marrow lesions, cartilage defects, osteophytes, Hoffa's synovitis, and effusion synovitis), were also performed. All clinical and imaging evaluations were performed preoperatively and 12 months postoperatively and compared between the groups. In demographic data, no significant differences were found between the two groups. The total score of KOOS at 12 months postoperatively was significantly more favorable than the preoperative score in the high-dose groups. Pain and symptoms subscale scores of KOOS at 12 months postoperatively were significantly better in the high-dose group than in the low-dose group. The bone marrow lesions, Hoffa's synovitis, and effusion synovitis improved approximately 30-40% at 12 months postoperatively compared to baseline in both groups. However, there were no significant differences in imaging evaluations between the two groups. In conclusion, the pain and symptoms subscale scores of KOOS from baseline to 12 months postoperatively improved better in the high-dose group than in the low-dose group. Our findings suggest that intra-articular injection of SVF cells for knee OA is an innovative approach.
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Affiliation(s)
- Masanori Tsubosaka
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Tomoyuki Matsumoto
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Satoshi Sobajima
- Department of Orthopaedic Surgery, Sobajima Clinic, Higashiosaka, Osaka
| | - Takehiko Matsushita
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Hideki Iwaguro
- Department of Orthopaedic Surgery, Sobajima Clinic, Higashiosaka, Osaka
| | - Ryosuke Kuroda
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
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Nie F, Bi H, Zhang C, Ding P. Differentiation potential and mRNA profiles of human dedifferentiated adipose cells and adipose‑derived stem cells from young donors. Mol Med Rep 2020; 23:47. [PMID: 33200799 PMCID: PMC7705993 DOI: 10.3892/mmr.2020.11685] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2020] [Accepted: 10/27/2020] [Indexed: 12/14/2022] Open
Abstract
Dedifferentiated adipose cells (DAs) and adipose-derived stem cells (ADSCs) are two of the primary types of stem cells derived from adipose tissue, which have been reported to possess similar characteristics, but also exhibit unique phenotypic and functional advantages. However, several reports have described inconsistent results regarding their differences in multilineage differentiation function. Moreover, to the best of our knowledge, there are no studies assessing their myogenic ability, or the differences in the transcriptome between the two cell types derived from lipoaspirates via tumescent liposuction from the same donors. The aim of the present study was to compare the properties and expression profiles of these cell types. Subcutaneous adipose tissue of three female patients (aged 23–30 years) with a physiological BMI (19.1–23.9 kg/m2) were obtained during tumescent liposuction of the abdomen or the thigh. The stromal vascular fraction and mature adipocytes were obtained via collagenase digestion, and ADSCs and DAs were cultured successively. To determine the differences between DAs and ADSCs after 6–7 passages, cell proliferation assays, phenotypic assessment, differentiation assays and high-throughput RNA sequencing (seq) were used. Similar cell morphologies, proliferation dynamics, surface markers and transcriptome expression profiles were observed between the DAs and ADSCs. Whilst there were notable individual differences in the osteogenic, lipogenic, chondrogenic and myogenic abilities of the DAs and ADSCs, it was difficult to determine their differentiation potential based only on the cell source. Interestingly, the myogenic ability was relatively stronger in cells with relatively weaker lipogenic ability. Only 186 differentially expressed genes between the two groups were identified using RNAseq. Several of these genes were involved in biological functions such as transcription regulation, protein translation regulation, cytokine interactions and energy metabolism regulation. The results of the present study suggested a similar functional potential of DAs and ADSCs from young donors undergoing tumescent liposuction operation in regeneration areas and the balance of the differentiative ability of the same cell populations. These data may provide a foundation for further clinical administration of stem cells derived from adipose tissues in therapy.
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Affiliation(s)
- Fangfei Nie
- Department of Plastic Surgery, Peking University Third Hospital, Beijing 100191, P.R. China
| | - Hongsen Bi
- Department of Plastic Surgery, Peking University Third Hospital, Beijing 100191, P.R. China
| | - Chen Zhang
- Department of Plastic Surgery, Peking University Third Hospital, Beijing 100191, P.R. China
| | - Pengbing Ding
- Department of Plastic Surgery, Peking University Third Hospital, Beijing 100191, P.R. China
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