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Arena A, Troise S, De Francesco F, Apolito M, Committeri U, Salzano G, Romano A, Bonavolontà P, Abbate V, Nocini R, Dell'Aversana Orabona G. Fat Graft as Regenerative Treatment of Facial Manifestations of Systemic Sclerosis: A Systematic Review on the Role of Adipose Tissue-Derived Stem Cells and on Surgical Outcomes to Define a New Standardised Injection Protocol. Wound Repair Regen 2025; 33:e70045. [PMID: 40387444 DOI: 10.1111/wrr.70045] [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: 01/02/2025] [Accepted: 05/06/2025] [Indexed: 05/20/2025]
Abstract
Facial symptoms of systemic sclerosis (SSc)-such as reduced skin elasticity, fibrosis and microstomy-significantly impact quality of life. In recent years, autologous fat grafting has emerged as a promising treatment for these issues, but determining the optimal timing and techniques for fat injection remains a challenge for surgeons. Our study aimed to perform a systematic review of the available literature to establish a standardised protocol for this procedure. We reviewed all relevant studies published up to 18 August 2023, focusing specifically on diffuse facial scleroderma. In addition to clinical reports, we included articles discussing the pathophysiological mechanisms behind the effects of adipose stem cells. A total of 18 articles were analysed, revealing a range of methods and timelines for the procedure. The volume of fat injected varied from 6 cc for perioral treatment to 72 cc for a full-face approach, with treatment intervals ranging from one session per year to one every 3 months. On average, around 50% of the fat was reabsorbed within 6 months. Adipose stem cells were identified as a key factor in both tissue regeneration and fat resorption rates. This review supports the effectiveness of autologous fat grafting for facial scleroderma, emphasising the role of adipose stem cells. For optimal results, two procedures spaced 3-6 months apart, followed by annual maintenance, are recommended. Consistent fat volumes in different facial areas are essential to achieve longer-lasting outcomes and minimise resorption.
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Affiliation(s)
- A Arena
- Maxillofacial Surgery Unit, Department of Neurosciences, Reproductive and Odontostomatological Sciences, University Federico II of Naples, Naples, Italy
| | - S Troise
- Maxillofacial Surgery Unit, Department of Neurosciences, Reproductive and Odontostomatological Sciences, University Federico II of Naples, Naples, Italy
| | - F De Francesco
- Department of Reconstructive Surgery and Hand Surgery, AOU 'Ospedali Riuniti, Ancona, Italy
- Accademia del Lipofilling, Research and Training Center in Regenerative Surgery, Jesi, Italy
| | - M Apolito
- Maxillofacial Surgery Unit, Department of Neurosciences, Reproductive and Odontostomatological Sciences, University Federico II of Naples, Naples, Italy
| | - U Committeri
- Maxillofacial Surgery Unit, University Hospital of Terni, Terni, Italy
| | - G Salzano
- Maxillofacial Surgery Unit, Department of Neurosciences, Reproductive and Odontostomatological Sciences, University Federico II of Naples, Naples, Italy
| | - A Romano
- Maxillofacial Surgery Unit, Department of Neurosciences, Reproductive and Odontostomatological Sciences, University Federico II of Naples, Naples, Italy
| | - P Bonavolontà
- Maxillofacial Surgery Unit, Department of Neurosciences, Reproductive and Odontostomatological Sciences, University Federico II of Naples, Naples, Italy
| | - V Abbate
- Maxillofacial Surgery Unit, Department of Neurosciences, Reproductive and Odontostomatological Sciences, University Federico II of Naples, Naples, Italy
| | - R Nocini
- Department of Otorhinolaryngology, University Hospital of Verona, Verona, Italy
| | - G Dell'Aversana Orabona
- Maxillofacial Surgery Unit, Department of Neurosciences, Reproductive and Odontostomatological Sciences, University Federico II of Naples, Naples, Italy
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Storti G, Foti R, Foti R, Palmesano M, Patacchiola M, Incognito D, Cervelli G, Longo B, Scioli MG, Fiorelli E, Terriaca S, Lisa A, Kim BS, Orlandi A, Cervelli V. A Comprehensive Exploration of the Biological Effects of Adipose-Derived Stem Cells in the Treatment of Systemic Sclerosis. Cells 2025; 14:458. [PMID: 40136706 PMCID: PMC11941144 DOI: 10.3390/cells14060458] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2025] [Revised: 03/10/2025] [Accepted: 03/17/2025] [Indexed: 03/27/2025] Open
Abstract
Systemic sclerosis (SSc) is a complex autoimmune disease characterized by vasculopathy and tissue fibrosis affecting the skin and internal organs. Genetic and environmental factors influence susceptibility, severity, and onset. Current treatments are limited and not always effective, leading researchers to investigate new approaches, such as the use of adipose-derived mesenchymal stem cells (ADSCs) through fat grafting. This review seeks to understand how ADSCs may impact the development and progression of SSc, with a particular focus on how these cells could alter immune responses and reduce fibrosis. ADSCs have been found to affect various immune cells, including T cells, B cells, macrophages, and dendritic cells, by releasing cytokines, chemokines, and growth factors. These interactions generally suppress inflammation and promote a regulatory immune environment. Additionally, ADSCs can influence the extracellular matrix, helping to prevent fibrosis through signaling molecules like exosomes. ADSCs show promise as a treatment for SSc due to their ability to modulate the immune system and reduce fibrosis. Early clinical studies are encouraging, but more research is needed to fully understand how they work and to develop effective treatment protocols.
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Affiliation(s)
- Gabriele Storti
- Plastic Surgery, Department of Surgical Sciences, University of Rome “Tor Vergata”, 00133 Rome, Italy; (G.S.); (M.P.); (M.P.); (B.L.); (V.C.)
| | - Riccardo Foti
- Plastic Surgery, Department of Surgical Sciences, University of Rome “Tor Vergata”, 00133 Rome, Italy; (G.S.); (M.P.); (M.P.); (B.L.); (V.C.)
| | - Roberta Foti
- Division of Rheumatology, A.O.U. “Policlinico-San Marco”, 95123 Catania, Italy;
- Department of Medicine and Surgery, University of Enna “Kore”, 94100 Enna, Italy
| | - Marco Palmesano
- Plastic Surgery, Department of Surgical Sciences, University of Rome “Tor Vergata”, 00133 Rome, Italy; (G.S.); (M.P.); (M.P.); (B.L.); (V.C.)
- PhD Program in Applied Medical Surgical Sciences, Department of Surgical Sciences, University of Rome “Tor Vergata”, Viale Oxford 81, 00133 Rome, Italy;
| | - Martina Patacchiola
- Plastic Surgery, Department of Surgical Sciences, University of Rome “Tor Vergata”, 00133 Rome, Italy; (G.S.); (M.P.); (M.P.); (B.L.); (V.C.)
| | - Dalila Incognito
- Medical Oncology Unit, Department of Human Pathology “G. Barresi”, University of Messina, 98122 Messina, Italy;
| | - Giulio Cervelli
- Department of Experimental Medicine, University of Rome “Tor Vergata”, 00133 Rome, Italy;
| | - Benedetto Longo
- Plastic Surgery, Department of Surgical Sciences, University of Rome “Tor Vergata”, 00133 Rome, Italy; (G.S.); (M.P.); (M.P.); (B.L.); (V.C.)
| | - Maria Giovanna Scioli
- Anatomy Pathology Institute, Department of Biomedicine and Prevention, University of Rome “Tor Vergata”, 00133 Rome, Italy; (M.G.S.); (E.F.); (S.T.); (A.O.)
| | - Elena Fiorelli
- Anatomy Pathology Institute, Department of Biomedicine and Prevention, University of Rome “Tor Vergata”, 00133 Rome, Italy; (M.G.S.); (E.F.); (S.T.); (A.O.)
| | - Sonia Terriaca
- Anatomy Pathology Institute, Department of Biomedicine and Prevention, University of Rome “Tor Vergata”, 00133 Rome, Italy; (M.G.S.); (E.F.); (S.T.); (A.O.)
| | - Andrea Lisa
- PhD Program in Applied Medical Surgical Sciences, Department of Surgical Sciences, University of Rome “Tor Vergata”, Viale Oxford 81, 00133 Rome, Italy;
- Department of Plastic and Reconstructive Surgery, European Institute of Oncology, IRCCS, 20139 Milan, Italy
- Department of Biomedical Sciences, Humanitas University, 20072 Milan, Italy
| | - Bong Sung Kim
- Department of Plastic Surgery and Hand Surgery, University Hospital Zurich, 8006 Zurich, Switzerland;
| | - Augusto Orlandi
- Anatomy Pathology Institute, Department of Biomedicine and Prevention, University of Rome “Tor Vergata”, 00133 Rome, Italy; (M.G.S.); (E.F.); (S.T.); (A.O.)
| | - Valerio Cervelli
- Plastic Surgery, Department of Surgical Sciences, University of Rome “Tor Vergata”, 00133 Rome, Italy; (G.S.); (M.P.); (M.P.); (B.L.); (V.C.)
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Nilforoushzadeh MA, Heidari A, Ghane Y, Hosseini S, Azizi H, Najar Nobari N, Heidari N. Efficacy and safety of platelet-rich plasma therapy in systemic sclerosis and localized scleroderma; a systematic review. Arch Dermatol Res 2025; 317:504. [PMID: 40014116 DOI: 10.1007/s00403-025-03934-4] [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: 08/01/2024] [Revised: 01/21/2025] [Accepted: 01/27/2025] [Indexed: 02/28/2025]
Abstract
Systemic sclerosis (SSc) and localized scleroderma (LoSc) are rare connective tissue diseases that are identified by skin thickening and hardening with different mechanisms of action. Although advancements in treatments have been achieved in recent years, these conditions remain a major cause of morbidity and currently lack a definitive cure. We sought to evaluate the efficacy and safety of platelet-rich plasma (PRP) treatment in individuals with LoSc and SSc. PubMed/Medline, Ovid-Embase, and Web of Science were systematically searched until December 27th, 2024. A citation search was also carried out, and clinical studies published in English were eligible to be included. A total of 11 studies utilized PRP to treat different conditions of scleroderma. In limited and diffuse forms of SSc, PRP resulted in the improvement of mouth handicap in systemic sclerosis (MHISS) items, skin elasticity, skin ulcer healing, and vascularization both alone and alongside hyaluronic acid, autologous fat, and stromal vascular fraction. Moreover, PRP injections led to a significant decrease in the LoSc cutaneous assessment tool (LoSCAT), as well as a reduction in pain and disease symptoms. Furthermore, patients with en coupe de sabre experienced hair regrowth after PRP treatment. The adverse effects, which can be limited or diffuse, were mild and self-limited. PRP contains a considerable number of platelets, cytokines, and growth factors. PRP is considered a safe supplementary treatment option alongside standard therapy for both LoSc and SSc, with the potential to promote improvement in these patients, either as a standalone therapy or in conjunction with other therapeutic approaches.
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Affiliation(s)
- Mohammad Ali Nilforoushzadeh
- Skin Repair Research Center, Jordan Dermatology and Hair Transplantation Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Skin and Stem Cell Research Center, Tehran University of Medical Sciences, Tehran, 1449614535, Iran
| | - Amirhossein Heidari
- Skin Repair Research Center, Jordan Dermatology and Hair Transplantation Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Skin and Stem Cell Research Center, Tehran University of Medical Sciences, Tehran, 1449614535, Iran
- Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Yekta Ghane
- Skin Repair Research Center, Jordan Dermatology and Hair Transplantation Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Skin and Stem Cell Research Center, Tehran University of Medical Sciences, Tehran, 1449614535, Iran
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Seyedayin Hosseini
- Skin Repair Research Center, Jordan Dermatology and Hair Transplantation Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Skin and Stem Cell Research Center, Tehran University of Medical Sciences, Tehran, 1449614535, Iran
- School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hanieh Azizi
- Skin Repair Research Center, Jordan Dermatology and Hair Transplantation Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Skin and Stem Cell Research Center, Tehran University of Medical Sciences, Tehran, 1449614535, Iran
| | - Niloufar Najar Nobari
- Skin Repair Research Center, Jordan Dermatology and Hair Transplantation Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
- Skin and Stem Cell Research Center, Tehran University of Medical Sciences, Tehran, 1449614535, Iran.
| | - Nazila Heidari
- Skin Repair Research Center, Jordan Dermatology and Hair Transplantation Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
- Skin and Stem Cell Research Center, Tehran University of Medical Sciences, Tehran, 1449614535, Iran.
- School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
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Li L, He Y, Zhao J, Yin H, Feng X, Fan X, Wu W, Lu Q. Mesenchymal Stromal Cell-Based Therapy: A Promising Approach for Autoimmune Diseases. Clin Rev Allergy Immunol 2025; 68:21. [PMID: 39982546 DOI: 10.1007/s12016-025-09030-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/04/2025] [Indexed: 02/22/2025]
Abstract
Autoimmune diseases are characterized by immune dysregulation, resulting in aberrant reactivity of T cells and antibodies to self-antigens, leading to various patterns of inflammation and organ dysfunction. However, current therapeutic agents exhibit broad-spectrum activity and lack disease-specific selectivity, leading to enduring adverse effects, notably severe infections, and malignancies, and patients often fail to achieve the intended clinical goals. Mesenchymal stromal cells (MSCs) are multipotent stromal cells that can be easily derived from various tissues, such as adipose tissue, umbilical cords, Wharton's jelly, placenta, and dental tissues. MSCs offer advantages due to their immunomodulatory and anti-inflammatory abilities, low immunogenicity, and a high capacity for proliferation and multipotent differentiation, making them excellent candidates for cell-based treatment in autoimmune disorders. This review will cover preclinical studies and clinical trials involving MSCs in autoimmune diseases, as well as the primary challenges associated with the clinical application of MSC therapies and strategies for maximizing their therapeutic potential.
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Affiliation(s)
- Liming Li
- Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China
- Key Laboratory of Basic and Translational Research On Immune-Mediated Skin Diseases, Chinese Academy of Medical Sciences, Nanjing, China
| | - Yong He
- Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China
| | - Junpeng Zhao
- Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China
- Key Laboratory of Basic and Translational Research On Immune-Mediated Skin Diseases, Chinese Academy of Medical Sciences, Nanjing, China
- Department of Clinical Laboratory, Xiangya Hospital, Central South University, Changsha, China
| | - Huiqi Yin
- Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China
- Key Laboratory of Basic and Translational Research On Immune-Mediated Skin Diseases, Chinese Academy of Medical Sciences, Nanjing, China
| | - Xiwei Feng
- Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China
- Key Laboratory of Basic and Translational Research On Immune-Mediated Skin Diseases, Chinese Academy of Medical Sciences, Nanjing, China
| | - Xinyu Fan
- Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China
- Key Laboratory of Basic and Translational Research On Immune-Mediated Skin Diseases, Chinese Academy of Medical Sciences, Nanjing, China
| | - Wei Wu
- Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China
- Key Laboratory of Basic and Translational Research On Immune-Mediated Skin Diseases, Chinese Academy of Medical Sciences, Nanjing, China
| | - Qianjin Lu
- Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China.
- Key Laboratory of Basic and Translational Research On Immune-Mediated Skin Diseases, Chinese Academy of Medical Sciences, Nanjing, China.
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Yessirkepov M, Fedorchenko Y, Zimba O, Mukanova U. Use of platelet-rich plasma in rheumatic diseases. Rheumatol Int 2024; 45:13. [PMID: 39739042 DOI: 10.1007/s00296-024-05776-1] [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: 11/26/2024] [Accepted: 12/23/2024] [Indexed: 01/02/2025]
Abstract
Platelet-rich plasma (PRP) has gained increasing recognition as a promising therapeutic agent in managing rheumatic diseases. Conventional treatments, including nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and disease-modifying antirheumatic drugs (DMARDs), primarily act on reducing inflammation but fail to address the underlying mechanisms of connective tissue degradation. PRP, an autologous preparation enriched with growth factors and bioactive molecules, is pivotal in modulating inflammation and fostering tissue regeneration. This review overviews the therapeutic potential of PRP across a spectrum of rheumatic diseases, such as osteoarthritis (OA), rheumatoid arthritis (RA), systemic sclerosis (SSc), and osteonecrosis. The regenerative capacity of PRP, driven by vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and transforming growth factor-beta (TGF-β), promotes tissue repair, reduces cartilage damage and improves joint function. Emerging evidence supports the efficacy of PRP in early-stage OA, demonstrating superior outcomes over traditional therapies like hyaluronic acid and glucocorticoids in terms of pain relief and functional improvement. Despite its benefits, PRP therapy is characterized by variability in treatment responses, with challenges in standardizing preparation protocols and treatment regimens. This review highlights the need for robust clinical trials to establish uniform treatment protocols, optimize patient selection, and evaluate the long-term clinical outcomes of PRP therapy in rheumatic diseases.
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Affiliation(s)
- Marlen Yessirkepov
- Department of Biology and Biochemistry, South Kazakhstan Medical Academy, Shymkent, Kazakhstan
| | - Yuliya Fedorchenko
- Department of Pathophysiology, Ivano-Frankivsk National Medical University, Halytska Str. 2, Ivano-Frankivsk, 76018, Ukraine.
| | - Olena Zimba
- Department of Rheumatology, Immunology and Internal Medicine, University Hospital in Kraków, Kraków, Poland
- National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, Poland
- Department of Internal Medicine N2, Danylo Halytsky Lviv National Medical University, Lviv, Ukraine
| | - Ulzhan Mukanova
- Department of Surgery and Anesthesiology-Intensive Care, Khoja Akhmet Yassawi International Kazakh-Turkish University, Shymkent, Kazakhstan
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Almadori A, Fung SC, Denton CP, Butler PEM. Fat Grafting and Adipose Stem Cells for Facial Systemic Sclerosis: A Systematic Review of the Literature. Aesthet Surg J 2024; 45:NP25-NP30. [PMID: 39325728 PMCID: PMC11634384 DOI: 10.1093/asj/sjae200] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2024] [Revised: 09/11/2024] [Accepted: 09/25/2024] [Indexed: 09/28/2024] Open
Abstract
BACKGROUND Orofacial modifications occurring in systemic sclerosis are detrimental for patients, but the therapeutic options are limited. OBJECTIVES This systematic review aimed to perform an up-to-date appraisal of the literature focusing on fat grafting and other adipose stem cell-based therapies for the treatment of facial systemic sclerosis, determining its efficacy and safety, and investigating the current practice for treatment optimization. METHODS The review was prospectively registered in PROSPERO (CRD42021286268) and followed the PRISMA principles. Multiple databases were searched and only original studies were included. RESULTS Over the 12 studies matching the inclusion criteria, 174 patients were treated. Of these, 87.3% (n = 152) were considered to have improved. The complications, graded with the Clavien-Dindo grading system, were Grade 1 (no treatment required) or Grade 2 (antibiotic required). Patients received a mean [standard deviation] of 2.5 [3.68] (median, 1.35; range, 1-14) lipotransfer procedures. Overall, an average volume of 14.60 [6.24] mL was injected in the facial area (median, 16 mL; range, 3-27 mL). The average interval between procedures was 5.30 [2.04] months (median, 6 months; range 3-6.91 months). At the time of inclusion, patients were diagnosed with scleroderma disease on average after 14.7 [7.35] years. CONCLUSIONS Fat grafting for facial systemic sclerosis is effective and safe. The definitive durability of the effect is still unclear, and the optimal number of treatments must be determined to define a precise evidence-based protocol. The body of evidence is highly fragmented, with disagreements over surgical techniques and outcome assessments, making results from different studies often not comparable. The level of evidence is overall low or very low, and the risk of bias of published studies is overall medium to high. Randomized controlled trials are urgently needed. LEVEL OF EVIDENCE: 3 (THERAPEUTIC)
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Affiliation(s)
- Aurora Almadori
- Corresponding Author: Dr Aurora Almadori, Royal Free Hospital, 9th Floor (East), 2QG, 10 Pond St, London NW3 2PS, UK. E-mail:
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Condorelli AG, Paganelli A, Marraccini C, Ficarelli E, Motolese A, Contu L, Motolese A. Platelet-rich plasma for the treatment of scleroderma-associated ulcers: a single-center experience and literature review. Dermatol Reports 2024; 16:9878. [PMID: 39539989 PMCID: PMC11558311 DOI: 10.4081/dr.2024.9878] [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: 10/20/2023] [Accepted: 02/04/2024] [Indexed: 11/16/2024] Open
Abstract
Systemic sclerosis (SS) is a complex connective tissue disease characterized by vasculopathy and progressive fibrosis, primarily considered an autoimmune disorder. SS can affect multiple organs and tissues, including the skin, respiratory, gastrointestinal, genitourinary, cardiovascular, and musculoskeletal systems. Skin involvement is common, and SS-related ulcers, especially digital ulcers, occur in roughly 50% of patients. These ulcers not only cause pain but also significantly impact patients' quality of life, and in severe cases, they can lead to infection, gangrene, and amputation. The search for novel therapies for scleroderma-related ulcers remains an ongoing research area. Platelet-rich plasma (PRP) has been investigated as a potential treatment for difficult-to-heal ulcers, including diabetic, pressure, and vascular ulcers. In this study, we share our experience in treating scleroderma ulcers with PRP. Ten patients with confirmed SS and chronic skin ulcers lasting at least six weeks, which had not responded to conventional treatments, were selected for the study. Homologous PRP gel was prepared and applied once a week for up to eight weeks. The ulcers were documented photographically before and after PRP treatment, and pain levels were assessed using a visual analog scale (VAS). We also conducted a systematic review of the literature focusing on the use of PRP in the setting of SS. The results from our casuistry showed that the ten patients, including eight females and two males with a median age of 52.5 years, had ulcer sizes ranging from 0.78 cm2 to 28.26 cm2. The ulcers were located on fingers, legs, and heels, and they were associated with various forms of SS, including limited and diffuse cutaneous involvement. Raynaud's phenomenon was prevalent, and two patients exhibited organ involvement. The average ulcer size at the end of PRP treatment decreased significantly, with a 78% reduction in ulcered area. Pain levels also markedly improved, as indicated by a reduction in VAS scores. With regards to systematic revision of literature, we retrieved 45 cases of SS treated with PRP-based therapeutic regimes. However, only a minority of them (n=16) underwent PRP treatment for the treatment of SS-related ulcers. An improvement in wound size and pain has been documented in all cases. Taken together, these data highlight the potential benefits of using homologous PRP in the treatment of scleroderma ulcers, emphasizing its positive impact on ulcer size reduction and pain relief.
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Affiliation(s)
| | - Alessia Paganelli
- Dermatology Unit, Reggio Emilia AUSL-IRCCS, Arcispedale Santa Maria Nuova, Reggio Emilia
| | | | - Elena Ficarelli
- Dermatology Unit, Reggio Emilia AUSL-IRCCS, Arcispedale Santa Maria Nuova, Reggio Emilia
| | - Alfonso Motolese
- Section of Dermatology, Department of Clinical and Experimental Medicine, University of Messina, Italy
| | - Luca Contu
- Dermatology Unit, Reggio Emilia AUSL-IRCCS, Arcispedale Santa Maria Nuova, Reggio Emilia
| | - Alberico Motolese
- Dermatology Unit, Reggio Emilia AUSL-IRCCS, Arcispedale Santa Maria Nuova, Reggio Emilia
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Xu N, Li L, Zou J, Yue W, Wang P, Chai M, Li L, Zhang L, Li X, Cheng Y, Wang Z, Wang X, Wang R, Xiang J, Linghu E, Chai N. PRP improves the outcomes of autologous skin graft transplantation on the esophagus by promoting angiogenesis and inhibiting fibrosis and inflammation. J Transl Int Med 2024; 12:384-394. [PMID: 39360159 PMCID: PMC11444473 DOI: 10.2478/jtim-2023-0126] [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] [Indexed: 10/04/2024] Open
Abstract
BACKGROUND AND OBJECTIVES Autologous skin graft (ASG) transplantation is a challenging approach but a promising option for patients to prevent postoperative esophageal stricture. Nonetheless, the current strategies require improvement. We aimed to investigate the effectiveness of the injection of platelet-rich plasma (PRP) before skin graft transplantation for extensive esophageal defects after endoscopic resection. METHODS Standardized complete circular endoscopic resection (5 cm in length) was performed in 27 pigs allocated into 3 groups. The artificial ulcers were treated with a fully covered esophageal stent (control group), ASG (ASG group), and submucosal injection of PRP with ASG (PRP-ASG group). Macroscopic evaluation and histological analysis of the remolded esophagus were performed 7, 14, and 28 days after surgery. RESULTS The macroscopic evaluation indicated that submucosal injection of PRP before transplantation effectively promoted the survival rate of skin grafts and decreased the rate of mucosal contraction compared with those treated with ASG or stent alone. Histological analysis of submucosal tissue showed that this modified strategy significantly promoted wound healing of reconstructed tissues by enhancing angiogenesis, facilitating collagen deposition, and decreasing inflammation and fibrogenesis. CONCLUSIONS These findings suggested that PRP might be used as a biological supplement to increase the esophageal skin graft survival rate and improve submucosal tissue remolding in a clinically relevant porcine model. With extremely low mucosal contraction, this novel combination strategy showed the potential to effectively prevent stenosis in extensive esophageal ulcers.
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Affiliation(s)
- Ning Xu
- Senior Department of Gastroenterology, The First Medical Center of PLA General Hospital, Beijing100853, Beijing, China
| | - Longsong Li
- Senior Department of Gastroenterology, The First Medical Center of PLA General Hospital, Beijing100853, Beijing, China
| | - Jiale Zou
- Senior Department of Gastroenterology, The First Medical Center of PLA General Hospital, Beijing100853, Beijing, China
| | - Wenyi Yue
- Department of Radiology, Chinese PLA General Medical School, Beijing100853, Beijing, China
| | - Pengju Wang
- Senior Department of Gastroenterology, The First Medical Center of PLA General Hospital, Beijing100853, Beijing, China
| | - Mi Chai
- Department of Plastic Surgery, The First Medical Center of PLA General Hospital, Beijing100853, Beijing, China
| | - Li Li
- Department of Plastic Surgery, The First Medical Center of PLA General Hospital, Beijing100853, Beijing, China
| | - Lihua Zhang
- Department of Pathology, The Fourth Medical Center of PLA General Hospital, Beijing100853, Beijing, China
| | - Xiao Li
- Senior Department of Gastroenterology, The First Medical Center of PLA General Hospital, Beijing100853, Beijing, China
| | - Yaxuan Cheng
- Senior Department of Gastroenterology, The First Medical Center of PLA General Hospital, Beijing100853, Beijing, China
| | - Zixin Wang
- Senior Department of Gastroenterology, The First Medical Center of PLA General Hospital, Beijing100853, Beijing, China
| | - Xueting Wang
- Senior Department of Gastroenterology, The First Medical Center of PLA General Hospital, Beijing100853, Beijing, China
| | - Runzi Wang
- Senior Department of Gastroenterology, The First Medical Center of PLA General Hospital, Beijing100853, Beijing, China
| | - Jingyuan Xiang
- Senior Department of Gastroenterology, The First Medical Center of PLA General Hospital, Beijing100853, Beijing, China
| | - Enqiang Linghu
- Senior Department of Gastroenterology, The First Medical Center of PLA General Hospital, Beijing100853, Beijing, China
| | - Ningli Chai
- Senior Department of Gastroenterology, The First Medical Center of PLA General Hospital, Beijing100853, Beijing, China
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Swain HN, Boyce PD, Bromet BA, Barozinksy K, Hance L, Shields D, Olbricht GR, Semon JA. Mesenchymal stem cells in autoimmune disease: A systematic review and meta-analysis of pre-clinical studies. Biochimie 2024; 223:54-73. [PMID: 38657832 DOI: 10.1016/j.biochi.2024.04.009] [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: 01/30/2024] [Revised: 04/08/2024] [Accepted: 04/20/2024] [Indexed: 04/26/2024]
Abstract
Mesenchymal Stem Cells (MSCs) are of interest in the clinic because of their immunomodulation capabilities, capacity to act upstream of inflammation, and ability to sense metabolic environments. In standard physiologic conditions, they play a role in maintaining the homeostasis of tissues and organs; however, there is evidence that they can contribute to some autoimmune diseases. Gaining a deeper understanding of the factors that transition MSCs from their physiological function to a pathological role in their native environment, and elucidating mechanisms that reduce their therapeutic relevance in regenerative medicine, is essential. We conducted a Systematic Review and Meta-Analysis of human MSCs in preclinical studies of autoimmune disease, evaluating 60 studies that included 845 patient samples and 571 control samples. MSCs from any tissue source were included, and the study was limited to four autoimmune diseases: multiple sclerosis, rheumatoid arthritis, systemic sclerosis, and lupus. We developed a novel Risk of Bias tool to determine study quality for in vitro studies. Using the International Society for Cell & Gene Therapy's criteria to define an MSC, most studies reported no difference in morphology, adhesion, cell surface markers, or differentiation into bone, fat, or cartilage when comparing control and autoimmune MSCs. However, there were reported differences in proliferation. Additionally, 308 biomolecules were differentially expressed, and the abilities to migrate, invade, and form capillaries were decreased. The findings from this study could help to explain the pathogenic mechanisms of autoimmune disease and potentially lead to improved MSC-based therapeutic applications.
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Affiliation(s)
- Hailey N Swain
- Department of Biological Sciences, Missouri University of Science and Technology, USA
| | - Parker D Boyce
- Department of Biological Sciences, Missouri University of Science and Technology, USA
| | - Bradley A Bromet
- Department of Biological Sciences, Missouri University of Science and Technology, USA
| | - Kaiden Barozinksy
- Department of Biological Sciences, Missouri University of Science and Technology, USA
| | - Lacy Hance
- Department of Biological Sciences, Missouri University of Science and Technology, USA
| | - Dakota Shields
- Department of Mathematics and Statistics, Missouri University of Science and Technology, USA
| | - Gayla R Olbricht
- Department of Mathematics and Statistics, Missouri University of Science and Technology, USA
| | - Julie A Semon
- Department of Biological Sciences, Missouri University of Science and Technology, USA.
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10
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Kotani T, Saito T, Suzuka T, Matsuda S. Adipose-derived mesenchymal stem cell therapy for connective tissue diseases and complications. Inflamm Regen 2024; 44:35. [PMID: 39026275 PMCID: PMC11264739 DOI: 10.1186/s41232-024-00348-z] [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: 01/31/2024] [Accepted: 06/30/2024] [Indexed: 07/20/2024] Open
Abstract
Mesenchymal stem cells (MSCs) may be effective in treating connective tissue disease and associated organ damage, leveraging their anti-inflammatory and immunoregulatory effects. Moreover, MSCs may possess the ability to produce antiapoptotic, proliferative, growth, angiogenic, and antifibrotic factors. Among MSCs, adipose-derived MSCs (ASCs) stand out for their relative ease of harvesting and abundance. Additionally, studies have indicated that compared with bone marrow-derived MSCs, ASCs have superior immunomodulatory, proangiogenic, antiapoptotic, and antioxidative properties. However, relatively few reviews have focused on the efficacy of ASC therapy in treating connective tissue disease (CTD) and interstitial lung disease (ILD). Therefore, this review aims to evaluate evidence from preclinical studies that investigate the effectiveness of MSC therapy, specifically ASC therapy, in managing CTD and ILD. Moreover, we explore the outcomes of documented clinical trials. We also introduce an innovative approach involving the utilization of pharmacologically primed ASCs in the CTD model to address the current challenges associated with ASC therapy.
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Affiliation(s)
- Takuya Kotani
- Department of Internal Medicine (IV), Division of Rheumatology, Osaka Medical and Pharmaceutical University, Daigaku-Machi 2-7, Takatsuki, Osaka, 569-8686, Japan.
| | - Takashi Saito
- Department of Legal Medicine, Osaka Medical College, Takatsuki, Osaka, Japan
| | - Takayasu Suzuka
- Department of Internal Medicine (IV), Division of Rheumatology, Osaka Medical and Pharmaceutical University, Daigaku-Machi 2-7, Takatsuki, Osaka, 569-8686, Japan
| | - Shogo Matsuda
- Department of Internal Medicine (IV), Division of Rheumatology, Osaka Medical and Pharmaceutical University, Daigaku-Machi 2-7, Takatsuki, Osaka, 569-8686, Japan
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11
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Giammona A, Di Franco S, Lo Dico A, Stassi G. The miRNA Contribution in Adipocyte Maturation. Noncoding RNA 2024; 10:35. [PMID: 38921832 PMCID: PMC11206860 DOI: 10.3390/ncrna10030035] [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: 04/15/2024] [Revised: 05/30/2024] [Accepted: 06/07/2024] [Indexed: 06/27/2024] Open
Abstract
Mesenchymal stem cells, due to their multipotent ability, are considered one of the best candidates to be used in regenerative medicine. To date, the most used source is represented by the bone marrow, despite the limited number of cells and the painful/invasive procedure for collection. Therefore, the scientific community has investigated many alternative sources for the collection of mesenchymal stem cells, with the adipose tissue representing the best option, given the abundance of mesenchymal stem cells and the easy access. Although adipose mesenchymal stem cells have recently been investigated for their multipotency, the molecular mechanisms underlying their adipogenic potential are still unclear. In this scenario, this communication is aimed at defining the role of miRNAs in adipogenic potential of adipose-derived mesenchymal stem cells via real-time PCR. Even if preliminary, our data show that cell culture conditions affect the expression of specific miRNA involved in the adipogenic potential of mesenchymal stem cells. The in vitro/in vivo validation of these results could pave the way for novel therapeutic strategies in the field of regenerative medicine. In conclusion, our research highlights how specific cell culture conditions can modulate the adipogenic potential of adipose mesenchymal stem cells through the regulation of specific miRNAs.
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Affiliation(s)
- Alessandro Giammona
- Institute of Molecular Bioimaging and Physiology (IBFM), National Research Council (CNR), 20054 Segrate, Italy;
- National Biodiversity Future Center (NBFC), 90133 Palermo, Italy
- Laboratory of Cellular and Molecular Pathophysiology, Department of Precision Medicine in Medical, Surgical and Critical Care (Me.Pre.C.C.), University of Palermo, 90127 Palermo, Italy;
| | - Simone Di Franco
- Laboratory of Cellular and Molecular Pathophysiology, Department of Precision Medicine in Medical, Surgical and Critical Care (Me.Pre.C.C.), University of Palermo, 90127 Palermo, Italy;
| | - Alessia Lo Dico
- Institute of Molecular Bioimaging and Physiology (IBFM), National Research Council (CNR), 20054 Segrate, Italy;
- National Biodiversity Future Center (NBFC), 90133 Palermo, Italy
| | - Giorgio Stassi
- Laboratory of Cellular and Molecular Pathophysiology, Department of Precision Medicine in Medical, Surgical and Critical Care (Me.Pre.C.C.), University of Palermo, 90127 Palermo, Italy;
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12
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Almadori A, Butler PEM. Scarring and Skin Fibrosis Reversal with Regenerative Surgery and Stem Cell Therapy. Cells 2024; 13:443. [PMID: 38474408 PMCID: PMC10930731 DOI: 10.3390/cells13050443] [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: 01/16/2024] [Revised: 02/22/2024] [Accepted: 02/27/2024] [Indexed: 03/14/2024] Open
Abstract
Skin scarring and fibrosis affect millions of people worldwide, representing a serious clinical problem causing physical and psychological challenges for patients. Stem cell therapy and regenerative surgery represent a new area of treatment focused on promoting the body's natural ability to repair damaged tissue. Adipose-derived stem cells (ASCs) represent an optimal choice for practical regenerative medicine due to their abundance, autologous tissue origin, non-immunogenicity, and ease of access with minimal morbidity for patients. This review of the literature explores the current body of evidence around the use of ASCs-based regenerative strategies for the treatment of scarring and skin fibrosis, exploring the different surgical approaches and their application in multiple fibrotic skin conditions. Human, animal, and in vitro studies demonstrate that ASCs present potentialities in modifying scar tissue and fibrosis by suppressing extracellular matrix (ECM) synthesis and promoting the degradation of their constituents. Through softening skin fibrosis, function and overall quality of life may be considerably enhanced in different patient cohorts presenting with scar-related symptoms. The use of stem cell therapies for skin scar repair and regeneration represents a paradigm shift, offering potential alternative therapeutic avenues for fibrosis, a condition that currently lacks a cure.
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Affiliation(s)
- Aurora Almadori
- Centre for Nanotechnology and Regenerative Medicine, Division of Surgery & Interventional Science, University College of London, London NW3 2QG, UK;
- Department of Plastic Surgery, Royal Free London NHS Foundation Trust Hospital, London NW3 2QG, UK
- The Charles Wolfson Centre for Reconstructive Surgery, Royal Free Hospital Campus, University College of London, London NW3 2QG, UK
| | - Peter EM Butler
- Centre for Nanotechnology and Regenerative Medicine, Division of Surgery & Interventional Science, University College of London, London NW3 2QG, UK;
- Department of Plastic Surgery, Royal Free London NHS Foundation Trust Hospital, London NW3 2QG, UK
- The Charles Wolfson Centre for Reconstructive Surgery, Royal Free Hospital Campus, University College of London, London NW3 2QG, UK
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Sun T, Zhou C, Lu F, Dong Z, Gao J, Li B. Adipose-derived stem cells in immune-related skin disease: a review of current research and underlying mechanisms. Stem Cell Res Ther 2024; 15:37. [PMID: 38331803 PMCID: PMC10854049 DOI: 10.1186/s13287-023-03561-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Accepted: 11/06/2023] [Indexed: 02/10/2024] Open
Abstract
Adipose-derived stem cells (ASCs) are a critical adult stem cell subpopulation and are widely utilized in the fields of regenerative medicine and stem cell research due to their abundance, ease of harvest, and low immunogenicity. ASCs, which are homologous with skin by nature, can treat immune-related skin diseases by promoting skin regeneration and conferring immunosuppressive effects, with the latter being the most important therapeutic mechanism. ASCs regulate the immune response by direct cell-cell communication with immune cells, such as T cells, macrophages, and B cells. In addition to cell-cell interactions, ASCs modulate the immune response indirectly by secreting cytokines, interleukins, growth factors, and extracellular vesicles. The immunomodulatory effects of ASCs have been exploited to treat many immune-related skin diseases with good therapeutic outcomes. This article reviews the mechanisms underlying the immunomodulatory effects of ASCs, as well as progress in research on immune-related skin diseases.
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Affiliation(s)
- Tianyi Sun
- The Department of Plastic and Cosmetic Surgery, Nanfang Hospital, Southern Medical University, 1838 Guangzhou North Road, Guangzhou, 510515, Guangdong, China
| | - Cheng Zhou
- The Department of Plastic and Cosmetic Surgery, Nanfang Hospital, Southern Medical University, 1838 Guangzhou North Road, Guangzhou, 510515, Guangdong, China
| | - Feng Lu
- The Department of Plastic and Cosmetic Surgery, Nanfang Hospital, Southern Medical University, 1838 Guangzhou North Road, Guangzhou, 510515, Guangdong, China
| | - Ziqing Dong
- The Department of Plastic and Cosmetic Surgery, Nanfang Hospital, Southern Medical University, 1838 Guangzhou North Road, Guangzhou, 510515, Guangdong, China
| | - Jianhua Gao
- The Department of Plastic and Cosmetic Surgery, Nanfang Hospital, Southern Medical University, 1838 Guangzhou North Road, Guangzhou, 510515, Guangdong, China.
| | - Bin Li
- The Department of Plastic and Cosmetic Surgery, Nanfang Hospital, Southern Medical University, 1838 Guangzhou North Road, Guangzhou, 510515, Guangdong, China.
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SULMIATI S, ISLAM AA, JOSH F, WARSINGGIH W, MAHMUDI A, HATTA M, NATZIR R, BUKHARI A, WAHYUNI S, PATELLONGI I. Effect of platelet-rich plasma plus stromal vascular fraction on epithelialization and collagenization of rectoanal wounds in Wistar rats. GAZZETTA MEDICA ITALIANA ARCHIVIO PER LE SCIENZE MEDICHE 2023; 182. [DOI: 10.23736/s0393-3660.23.05007-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2025]
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15
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Mercuri SR, Di Nicola MR, Bianchi VG, Paolino G. Adult-Onset Linear Morphea ( en coupe de sabre) of the Face Successfully Treated with Photoactivated Low-Temperature Platelet-Rich Plasma: A Valid Therapeutic Option. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:1114. [PMID: 37374318 DOI: 10.3390/medicina59061114] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Revised: 05/30/2023] [Accepted: 06/08/2023] [Indexed: 06/29/2023]
Abstract
Localized scleroderma (also known as morphea) is a chronic autoimmune disorder characterized by depressed, fibrotic, and dyschromic cutaneous lesions. It has a significant impact on the patient's daily life due to the unaesthetic evolution of the cutaneous lesions. Morphea is clinically divided into linear, circumscribed (plaque), generalized, pansclerotic, and mixed forms. Linear morphea en coupe de sabre (LM) usually arises in childhood. However, in about 32% of cases, it may arise in adulthood, showing a more aggressive course with also an increased risk of systemic involvement. Methotrexate is the first-line treatment for LM, although systemic steroids, topical agents (corticosteroids and calcineurin inhibitors), hyaluronic acid injections, and hydroxychloroquine or mycophenolate mofetil are valid therapeutic options. In any case, these treatments are not always effective and sometimes can be associated with important side effects and/or not tolerated by the patients. In this spectrum, platelet-rich plasma (PRP) injection can be considered a valid and safe alternative since PRP injections in the skin induce the release of anti-inflammatory cytokines and growth factors, thus reducing inflammation and increasing collagen remodeling. Herein, we describe a successful treatment of an adult-onset LM en coupe de sabre with photoactivated low-temperature PRP (Meta Cell Technology Plasma) sessions, showing an important local improvement of the lesion and patient satisfaction.
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Affiliation(s)
- Santo Raffaele Mercuri
- Unit of Dermatology and Cosmetology, I.R.C.C.S. San Raffaele Hospital, 20132 Milan, Italy
- Medicine and Surgery Faculty, San Raffaele Vita-Salute University, 20132 Milan, Italy
| | | | | | - Giovanni Paolino
- Unit of Dermatology and Cosmetology, I.R.C.C.S. San Raffaele Hospital, 20132 Milan, Italy
- Medicine and Surgery Faculty, San Raffaele Vita-Salute University, 20132 Milan, Italy
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16
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Wang HC, Li Z, Li Z, Wang X, Long X. Platelet-Rich Plasma Combined Fat Transplantation for the Treatment of Bleomycin-Induced Murine Scleroderma. Ann Plast Surg 2023; 90:626-630. [PMID: 37311318 DOI: 10.1097/sap.0000000000003579] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
BACKGROUND Low-fat retention induced by inflammation limits the clinical application of fat grafting for treating localized scleroderma (LS) patients. Novel methods to improve the therapeutic outcome are needed. OBJECTIVE The aim of the study is to investigate the effect of platelet-rich plasma (PRP)-assisted fat transplantation on skin fibrosis and adipose survival in the LS model. METHODS The LS model was established by the injection of bleomycin into BALB/C nude mice, which were randomly divided into the following 4 groups: healthy control, LS disease group model, fat transplantation group, and PRP+ fat transplantation group. The mice received a subcutaneous injection at back with phosphate-buffered saline, fat, or 20% PRP+ fat. Factors of immunoregulation, angiogenesis and adipogenesis were measured. RESULTS Platelet-rich plasma-combined fat transplantation significantly attenuated dermis fibrosis by reducing the production of type III collagen. The fat retention in the PRP+ fat transplantation group was 43 ± 4 mg, significantly higher than 22 ± 15 mg in the fat transplantation group (P = 0.0416). The level of tumor necrosis factor α and interleukin 2 showed no significant difference between the groups. The expression of angiogenesis factors, vascular endothelial growth factor, hepatocyte growth factor, platelet-derived growth factor, and CD31, significantly increased in the PRP+ fat transplantation group. The expression of adipogenesis factors, insulin-like growth factor 1 receptor, extracellular signal-regulated kinase, anti-CCAAT-enhancer-binding proteins, and peroxisome proliferator-activated receptor γ, also significantly increased in the PRP+ fat transplantation group. CONCLUSIONS The results demonstrated that PRP-combined fat transplantation attenuated dermis fibrosis and raised fat survival in the LS model by promoting angiogenesis and adipogenesis through insulin-like growth factor 1 receptor/extracellular signal-regulated kinase signaling pathway.
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Affiliation(s)
- Hayson Chenyu Wang
- From the Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai
| | - Zhijin Li
- Department of Plastic surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
| | - Zhujun Li
- Department of Plastic surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
| | - Xiaojun Wang
- Department of Plastic surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
| | - Xiao Long
- Department of Plastic surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
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Adipose Tissue and Adipose-Tissue-Derived Cell Therapies for the Treatment of the Face and Hands of Patients Suffering from Systemic Sclerosis. Biomedicines 2023; 11:biomedicines11020348. [PMID: 36830886 PMCID: PMC9953720 DOI: 10.3390/biomedicines11020348] [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: 12/30/2022] [Revised: 01/17/2023] [Accepted: 01/21/2023] [Indexed: 01/28/2023] Open
Abstract
Adipose tissue is recognized as a valuable source of cells with angiogenic, immunomodulatory, reparative and antifibrotic properties and emerged as a therapeutic alternative for the regeneration and repair of damaged tissues. The use of adipose-tissue-based therapy is expanding in autoimmune diseases, particularly in Systemic Sclerosis (SSc), a disease in which hands and face are severely affected, leading to disability and a decrease in quality of life. Combining the advantage of an abundant supply of fat tissue and a high abundance of stem/stromal cells, fat grafting and adipose tissue-derived cell-based therapies are attractive therapeutic options in SSc. This review aims to synthesize the evidence to determine the effects of the use of these biological products for face and hands treatment in the context of SSc. This highlights several points: the need to use relevant effectiveness criteria taking into account the clinical heterogeneity of SSc in order to facilitate assessment and comparison of innovative therapies; second, it reveals some impacts of the disease on fat-grafting success; third, an important heterogeneity was noticed regarding the manufacturing of the adipose-derived products and lastly, it shows a lack of robust evidence from controlled trials comparing adipose-derived products with standard care.
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18
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Autologous adipose-derived stromal vascular fraction and platelet concentrates for the treatment of complex perianal fistulas. Tech Coloproctol 2023; 27:135-143. [PMID: 36063257 PMCID: PMC9839808 DOI: 10.1007/s10151-022-02675-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2022] [Accepted: 07/27/2022] [Indexed: 01/18/2023]
Abstract
BACKGROUND Complex perianal fistulas are a major challenge for modern surgery since 10-35% of patients have functional problems after treatment. Sphincter-saving techniques have a wide range of efficacy (10-80%). We hypothesised that autologous adipose-derived stromal vascular fraction in combination with platelet rich plasma is a new therapeutic strategy with enhanced cure and function preservation rates. METHODS Adult patients with complex cryptoglandular perianal fistulas were treated with injection of autologous adipose-derived stromal vascular fraction in combination with platelet rich plasma around and inside the fistulous tract between May 2018 and April 2019 at the General and Emergency Surgery Operative Unit of the University Hospital "P. Giaccone" of Palermo. Fistulas were confirmed by magnetic resonance imaging. Patients completed the Short Form-36 score on quality of life and the Wexner and Vaizey scores on faecal incontinence, and they were functionally studied using a three-dimensional anorectal manometry. The clinical and functional follow-up was performed at 1 year and 2 years after surgery. RESULTS Nine patients (4 males, 5 females; median age 42 years [19-63 years]) with high trans-sphincteric or horseshoe fistulas were treated. The average number of previous surgeries per patient was 4.8. At 1 year follow-up, 77.7% of patients were cured, while at 2 years there was 1case of relapse. The variation in Short Form-36 score in cured patients was not significant (p = 0.0936). No statistically significant differences were found in continence scores. CONCLUSIONS The proposed treatment is a treatment option that preserves sphincter integrity and function, potentially avoiding postoperative incontinence and the need of repeated treatments.
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Jacobs A, Elghawy O, Baruqui DL, Elghawy AA. Current State of Platelet-rich Plasma in the Treatment of Rheumatic Disease: A Retrospective Review of the Literature. Curr Rheumatol Rev 2023; 19:400-407. [PMID: 37078351 PMCID: PMC10523354 DOI: 10.2174/1573397119666230420112017] [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: 09/25/2022] [Revised: 02/23/2023] [Accepted: 02/27/2023] [Indexed: 04/21/2023]
Abstract
INTRODUCTION Rheumatic diseases are a spectrum of autoimmune or inflammatory diseases that cause damage to the musculoskeletal system as well as vital organs, such as the heart, lungs, kidneys, and central nervous system. METHODS The study of rheumatic disease has made great progress in the understanding and management of these conditions in the last few decades using disease-modifying antirheumatic drugs and synthesized biological immunomodulating therapies. However, one potential treatment that has not been well investigated in rheumatic disease is platelet-rich plasma (PRP). PRP is proposed to facilitate the healing of injured tendons and ligaments through a variety of mechanisms, including mitogenesis, angiogenesis and macrophage activation via cytokine release, although its exact mechanism is unclear. RESULT There has been a great deal of work in determining the exact preparation method and composition of PRP for regenerative purposes in orthopedic surgery, sports medicine, dentistry, cardiac surgery, pediatric surgery, gynecology, urology, plastic surgery, ophthalmology, and dermatology. Despite this, there is a paucity of research on the impact of PRP on rheumatic disease. CONCLUSION This study aims to summarize and evaluate the current research concerning the use of PRP in rheumatic disease.
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Affiliation(s)
- Adam Jacobs
- Mount Sinai Medical Center, Miami Beach, FL, United States
| | - Omar Elghawy
- University of Virginia School of Medicine, Charlottesville, VA, United States
| | | | - Ahmed Aly Elghawy
- Department of Rheumatologic and Immunologic Disease, Cleveland Clinic, Cleveland, OH, United States
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Schipper JAM, Vriend L, Tuin AJ, Dijkstra PU, Schepers RH, van der Lei B, Jansma J, Harmsen MC. Supplementation of Facial Fat Grafting to Increase Volume Retention: A Systematic Review. Aesthet Surg J 2022; 42:NP711-NP727. [PMID: 35576617 PMCID: PMC9750673 DOI: 10.1093/asj/sjac122] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2022] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND For decades, facial fat grafting has been used in clinical practice for volume restoration. The main challenge of this technique is variable volume retention. The addition of supplements to augment fat grafts and increase volume retention has been reported in recent years. OBJECTIVES The aim of this systematic review was to investigate which supplements increase volume retention in facial fat grafting as assessed by volumetric outcomes and patient satisfaction. METHODS Embase, Medline, Ovid, Web of Science Core Collection, Cochrane Central Register of Controlled Trials, and Google Scholar were searched up to November 30, 2020. Only studies assessing volume after facial fat grafting with supplementation in human subjects were included. Outcomes of interest were volume or patient satisfaction. The quality of the studies was assessed with the Effective Public Health Practice Project tool. RESULTS After duplicates were removed 3724 studies were screened by title and abstract. After reading 95 full-text articles, 27 studies were eligible and included for comparison. Supplementation comprised of platelet-rich plasma, platelet-rich fibrin, adipose tissue-derived stromal cells or bone marrow-derived stromal cells, cellular or tissue stromal vascular fraction, or nanofat. In 13 out of 22 studies the supplemented group showed improved volumetric retention and 5 out of 16 studies showed greater satisfaction. The scientific quality of the studies was rated as weak for 20 of 27 studies, moderate for 6 of 27 studies, and strong for 1 study. CONCLUSIONS It remains unclear if additives contribute to facial fat graft retention and there is a need to standardize methodology. LEVEL OF EVIDENCE: 4
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Affiliation(s)
- Jan Aart M Schipper
- Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Linda Vriend
- Department of Plastic and Reconstructive Surgery, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
| | - Aartje J Tuin
- Department of Oral and Maxillofacial Surgery, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
| | - Pieter U Dijkstra
- Department of Rehabilitation Medicine, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
| | - Rutger H Schepers
- Department of Oral and Maxillofacial Surgery, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
| | - Berend van der Lei
- Department of Plastic and Reconstructive Surgery, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
| | - Johan Jansma
- Department of Oral and Maxillofacial Surgery, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
| | - Martin C Harmsen
- Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
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21
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Platelet-Rich Stroma (PRS) Injection Provides Great Improvement in Depressed Scars. Indian J Surg 2022. [DOI: 10.1007/s12262-022-03588-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
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22
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Abellan Lopez M, Philandrianos C, Daumas A, Velier M, Arcani R, Jouve E, Jaloux C, Bertrand B, Magalon J, Dignat-George F, Granel B, Casanova D, Sabatier F. Assessing the effect of PRP addition to facial micro-lipofilling for patients suffering from Scleroderma: A prospective routine care analysis. ANN CHIR PLAST ESTH 2022; 68:152-161. [PMID: 35987670 DOI: 10.1016/j.anplas.2022.07.016] [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: 04/25/2022] [Revised: 07/20/2022] [Accepted: 07/27/2022] [Indexed: 11/28/2022]
Abstract
BACKGROUND Combining fat graft with platelet derived products is now common practice in regenerative surgery. We proposed to assess the safety and efficacy of Platelet-Rich Plasma (PRP) addition to a micro-lipofilling protocol for facial treatment of patients suffering from Systemic Sclerosis (SSc). OBJECTIVE Main objective was to evaluate the improvement of the Mouth Handicap In Systemic Sclerosis (MHISS) scale score at 6 months post-therapy. METHOD Included SSc patients had a MHISS score equal or up to 20. Surgery was performed under general anesthesia. Micro-fat and PRP (CCA-NA from DEPA Classification) were mixed in a 70/30 ratio, before injection in peri-oral sites according to a specific protocol. Efficacy criteria were recorded at baseline, 3 and 6 months. Moreover, we compared this cohort (current study) to a former (2015) non-enriched micro-lipofilling cohort in the same indication, using the same protocol. RESULTS Thirteen women patients with mean age of 53.2 years (±14.3) have been included. At baseline, mean MHISS score was 29.5 (±8.7) and significantly decreased to 22.5 (±7.8) at 6 months (P=0.016), corresponding to a 22.0% of improvement from baseline, with a mean decrease of 6.5 points (±7.5) at 6 months. Patients received a mean volume of 30.8ml PRP-micro-fat (±8.1ml). CONCLUSION PRP addition appeared beneficial, however, controlled studies are required to determine its superiority to facial micro-lipofilling.
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Affiliation(s)
- M Abellan Lopez
- Plastic Surgery Department, La Conception Hospital, AP-HM, 13005 Marseille, France; Aix Marseille University, INSERM, INRA, C2VN, 13005 Marseille, France.
| | - C Philandrianos
- Plastic Surgery Department, La Conception Hospital, AP-HM, 13005 Marseille, France.
| | - A Daumas
- Internal Medicine Department, Assistance Publique Hôpitaux de Marseille (AP-HM), Aix-Marseille University, 13005 Marseille, France; Aix Marseille University, INSERM, INRA, C2VN, 13005 Marseille, France.
| | - M Velier
- Cell Therapy Department, Hôpital de la Conception, AP-HM, INSERM CIC BT 1409, 13005 Marseille, France; Aix Marseille University, INSERM, INRA, C2VN, 13005 Marseille, France.
| | - R Arcani
- Aix Marseille University, INSERM, INRA, C2VN, 13005 Marseille, France.
| | - E Jouve
- Service de Pharmacologie Clinique et Pharmacovigilance, Assistance Publique Hôpitaux de Marseille (AP-HM), CIC-CPCET, 13005 Marseille, France.
| | - C Jaloux
- Plastic Surgery Department, La Conception Hospital, AP-HM, 13005 Marseille, France.
| | - B Bertrand
- Plastic Surgery Department, La Conception Hospital, AP-HM, 13005 Marseille, France.
| | - J Magalon
- Cell Therapy Department, Hôpital de la Conception, AP-HM, INSERM CIC BT 1409, 13005 Marseille, France; Aix Marseille University, INSERM, INRA, C2VN, 13005 Marseille, France.
| | - F Dignat-George
- Cell Therapy Department, Hôpital de la Conception, AP-HM, INSERM CIC BT 1409, 13005 Marseille, France; Aix Marseille University, INSERM, INRA, C2VN, 13005 Marseille, France.
| | - B Granel
- Internal Medicine Department, Assistance Publique Hôpitaux de Marseille (AP-HM), Aix-Marseille University, 13005 Marseille, France.
| | - D Casanova
- Plastic Surgery Department, La Conception Hospital, AP-HM, 13005 Marseille, France.
| | - F Sabatier
- Cell Therapy Department, Hôpital de la Conception, AP-HM, INSERM CIC BT 1409, 13005 Marseille, France; Aix Marseille University, INSERM, INRA, C2VN, 13005 Marseille, France.
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Farina N, Benanti G, De Luca G, Palmisano A, Peretto G, Tomassetti S, Giorgione V, Forma O, Esposito A, Danese S, Dagna L, Matucci-Cerinic M, Campochiaro C. The Role of the Multidisciplinary Health Care Team in the Management of Patients with Systemic Sclerosis. J Multidiscip Healthc 2022; 15:815-824. [PMID: 35480063 PMCID: PMC9035450 DOI: 10.2147/jmdh.s295478] [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: 12/11/2021] [Accepted: 04/11/2022] [Indexed: 11/23/2022] Open
Abstract
Systemic sclerosis (SSc) is a rare connective tissue disease characterised by immune dysfunction, vascular damage and fibrosis affecting the skin and multiple internal organs. The clinical spectrum of SSc is wide and its manifestations may lead to severe morbidity and mortality, in addition to a great impact on patients' quality of life. Due to the multifaceted clinical manifestations of SSc, its management requires a combined expertise of different medical specialists to guarantee an adequate disease control and prevent organ complications. Multi-disciplinary teams (MDT), which are composed by physicians and other specialized health professionals, represent therefore a key element for the comprehensive management of SSc patients. Moreover, MTD can improve communication and patients' empowerment while the presence of dedicated nurses can help patients to ask questions about their condition. The scope of this narrative review is to analyse the available evidences regarding the role of MDT in the management of SSc patients, and how this holistic approach may improve different disease domains and the overall prognosis. MDT regarding the cardiovascular and lung complication are the more represented in literature, given the great impact in prognosis. Nonetheless, MDT have been shown to be fundamental also in other disease domains as they can intercept early manifestations, thus stratifying patients based on the individual risks in order to personalize patients' follow-up. MDTs may also minimize the treatment delay, enabling fast-track specialist referral. On the other hand, there are few trials specifically studying MDT in SSc and several authors have highlight the lack of standardization.
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Affiliation(s)
- Nicola Farina
- Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS San Raffaele Hospital, Milan, Italy
- School of Medicine, Vita-Salute San Raffaele University, Milan, Italy
| | - Giovanni Benanti
- Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS San Raffaele Hospital, Milan, Italy
- School of Medicine, Vita-Salute San Raffaele University, Milan, Italy
| | - Giacomo De Luca
- Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS San Raffaele Hospital, Milan, Italy
- School of Medicine, Vita-Salute San Raffaele University, Milan, Italy
| | - Anna Palmisano
- School of Medicine, Vita-Salute San Raffaele University, Milan, Italy
- Unit of Clinical and Experimental Radiology, IRCCS San Raffaele Hospital, Milan, Italy
| | - Giovanni Peretto
- Unit of Cardiac Electrophysiology and Arrhythmology, IRCCS San Raffaele Hospital, Milan, Italy
| | - Sara Tomassetti
- Department of Experimental and Clinical Medicine, Careggi University Hospital, Florence, Italy
| | - Veronica Giorgione
- Molecular and Clinical Sciences Research Institute, Fetal Medicine Unit, Department of Obstetrics and Gynaecology, St. George's University Hospitals NHS Foundation Trust, London, UK
| | - Ornella Forma
- Vulnology Nursing Service, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Antonio Esposito
- School of Medicine, Vita-Salute San Raffaele University, Milan, Italy
- Unit of Clinical and Experimental Radiology, IRCCS San Raffaele Hospital, Milan, Italy
| | - Silvio Danese
- School of Medicine, Vita-Salute San Raffaele University, Milan, Italy
- Unit of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, Milan, Italy
| | - Lorenzo Dagna
- Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS San Raffaele Hospital, Milan, Italy
- School of Medicine, Vita-Salute San Raffaele University, Milan, Italy
| | - Marco Matucci-Cerinic
- Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS San Raffaele Hospital, Milan, Italy
- Department of Experimental and Clinical Medicine, University of Florence and Division of Rheumatology AOUC, Florence, Italy
| | - Corrado Campochiaro
- Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS San Raffaele Hospital, Milan, Italy
- School of Medicine, Vita-Salute San Raffaele University, Milan, Italy
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Efficacy and safety of mesenchymal stem cells in the treatment of systemic sclerosis: a systematic review and meta-analysis. Stem Cell Res Ther 2022; 13:118. [PMID: 35313985 PMCID: PMC8935249 DOI: 10.1186/s13287-022-02786-3] [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: 11/09/2021] [Accepted: 02/17/2022] [Indexed: 11/28/2022] Open
Abstract
Background Systemic sclerosis (SSc) is an autoimmune disease with high morbidity and mortality characterized by fibrosis of the skin and internal organs. Some studies have investigated the use of stem cells to treat SSc. Herein, a systematic review and meta-analysis was conducted to determine the efficacy and safety of mesenchymal stem cells (MSCs) in the treatment of SSc. Methods PubMed, Embase, Cochrane Library, Web of Science, OVID, China National Knowledge Infrastructure and Wanfang databases were searched up to February 1, 2021. Literature screening, data extraction and quality assessment were conducted independently by two researchers in according to the inclusion and exclusion criteria. The discrepancies were resolved by a third researcher. Results A total of 9 studies encompassing 133 SSc patients were included in the study. Compared to the baseline after treatment with MSCs: 1. The modified Rodnan skin score (mRSS) was significantly reduced in patients with SSc (P < 0.00001). 2. MSCs decreased the number of digital ulcer, mouth handicap scale, and visual analog scale of hand pain in SSc patients (P = 0.0007 and P = 0.03, respectively). 3. No statistical differences were detected in Raynaud's condition score and Cochin hand function scale score at 6 months of MSCs therapy (P = 0.5 and P = 0.62). 4. After 12 months of follow-up, MSCs improve carbon monoxide diffusing capacity and forced vital capacity of SSc patients (P < 0.05). 5. Overall, MSCs application was safe; a few cases exhibited swelling at the injection site, diarrhea and arthralgia, which had self-recovery, and no severe adverse events occurred in the included trials. Conclusions MSC therapy improves the degree of skin thickening, lung function, and mouth opening and relieves finger ulcers and pain in patients with SSc without severe adverse events. Thus, MSCs or MSCs combined with plasma and traditional medicine might be an effective and promising treatment of SSc patients. PROSPERO registration number: CRD42020200350
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25
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Zanin-Silva DC, Santana-Gonçalves M, Kawashima-Vasconcelos MY, Oliveira MC. Management of Endothelial Dysfunction in Systemic Sclerosis: Current and Developing Strategies. Front Med (Lausanne) 2021; 8:788250. [PMID: 35004754 PMCID: PMC8727451 DOI: 10.3389/fmed.2021.788250] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2021] [Accepted: 11/29/2021] [Indexed: 12/12/2022] Open
Abstract
Systemic Sclerosis (SSc) is an autoimmune disease marked by dysregulation of the immune system, tissue fibrosis and dysfunction of the vasculature. Vascular damage, remodeling and inadequate endothelial repair are hallmarks of the disease. Since early stages of SSc, damage and apoptosis of endothelial cells (ECs) can lead to perivascular inflammation, oxidative stress and tissue hypoxia, resulting in multiple clinical manifestations. Raynaud's phenomenon, edematous puffy hands, digital ulcers, pulmonary artery hypertension, erectile dysfunction, scleroderma renal crisis and heart involvement severely affect quality of life and survival. Understanding pathogenic aspects and biomarkers that reflect endothelial damage in SSc is essential to guide therapeutic interventions. Treatment approaches described for SSc-associated vasculopathy include pharmacological options to improve blood flow and tissue perfusion and, more recently, cellular therapy to enhance endothelial repair, promote angiogenesis and heal injuries. This mini-review examines the current knowledge on cellular and molecular aspects of SSc vasculopathy, as well as established and developing therapeutic approaches for improving the vascular compartment.
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Affiliation(s)
- Djúlio César Zanin-Silva
- Center for Cell-Based Therapy, Regional Hemotherapy Center of the Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
- Basic and Applied Immunology Graduate Program, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
| | - Maynara Santana-Gonçalves
- Center for Cell-Based Therapy, Regional Hemotherapy Center of the Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
- Oncology, Stem Cell and Cell-Therapy Graduate Program, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
| | - Marianna Yumi Kawashima-Vasconcelos
- Center for Cell-Based Therapy, Regional Hemotherapy Center of the Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
- Internal Medicine Graduate Program, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
| | - Maria Carolina Oliveira
- Center for Cell-Based Therapy, Regional Hemotherapy Center of the Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
- Department of Internal Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
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Adipose stem cell niche reprograms the colorectal cancer stem cell metastatic machinery. Nat Commun 2021; 12:5006. [PMID: 34408135 PMCID: PMC8373975 DOI: 10.1038/s41467-021-25333-9] [Citation(s) in RCA: 49] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2020] [Accepted: 08/03/2021] [Indexed: 12/30/2022] Open
Abstract
Obesity is a strong risk factor for cancer progression, posing obesity-related cancer as one of the leading causes of death. Nevertheless, the molecular mechanisms that endow cancer cells with metastatic properties in patients affected by obesity remain unexplored. Here, we show that IL-6 and HGF, secreted by tumor neighboring visceral adipose stromal cells (V-ASCs), expand the metastatic colorectal (CR) cancer cell compartment (CD44v6 + ), which in turn secretes neurotrophins such as NGF and NT-3, and recruits adipose stem cells within tumor mass. Visceral adipose-derived factors promote vasculogenesis and the onset of metastatic dissemination by activation of STAT3, which inhibits miR-200a and enhances ZEB2 expression, effectively reprogramming CRC cells into a highly metastatic phenotype. Notably, obesity-associated tumor microenvironment provokes a transition in the transcriptomic expression profile of cells derived from the epithelial consensus molecular subtype (CMS2) CRC patients towards a mesenchymal subtype (CMS4). STAT3 pathway inhibition reduces ZEB2 expression and abrogates the metastatic growth sustained by adipose-released proteins. Together, our data suggest that targeting adipose factors in colorectal cancer patients with obesity may represent a therapeutic strategy for preventing metastatic disease. Obesity is a major risk factor for cancer related death. Here, the authors show that visceral adipose-derived factors promote vasculogenesis and metastatic dissemination by activation of STAT3, which inhibits miR-200a and enhances ZEB2 expression, effectively reprogramming colorectal cancer cells into a highly metastatic phenotype.
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Sierra-Sánchez Á, Montero-Vilchez T, Quiñones-Vico MI, Sanchez-Diaz M, Arias-Santiago S. Current Advanced Therapies Based on Human Mesenchymal Stem Cells for Skin Diseases. Front Cell Dev Biol 2021; 9:643125. [PMID: 33768095 PMCID: PMC7985058 DOI: 10.3389/fcell.2021.643125] [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: 12/17/2020] [Accepted: 02/18/2021] [Indexed: 12/17/2022] Open
Abstract
Skin disease may be related with immunological disorders, external aggressions, or genetic conditions. Injuries or cutaneous diseases such as wounds, burns, psoriasis, and scleroderma among others are common pathologies in dermatology, and in some cases, conventional treatments are ineffective. In recent years, advanced therapies using human mesenchymal stem cells (hMSCs) from different sources has emerged as a promising strategy for the treatment of many pathologies. Due to their properties; regenerative, immunomodulatory and differentiation capacities, they could be applied for the treatment of cutaneous diseases. In this review, a total of thirteen types of hMSCs used as advanced therapy have been analyzed, considering the last 5 years (2015-2020). The most investigated types were those isolated from umbilical cord blood (hUCB-MSCs), adipose tissue (hAT-MSCs) and bone marrow (hBM-MSCs). The most studied diseases were wounds and ulcers, burns and psoriasis. At preclinical level, in vivo studies with mice and rats were the main animal models used, and a wide range of types of hMSCs were used. Clinical studies analyzed revealed that cell therapy by intravenous administration was the advanced therapy preferred except in the case of wounds and burns where tissue engineering was also reported. Although in most of the clinical trials reviewed results have not been posted yet, safety was high and only local slight adverse events (mild nausea or abdominal pain) were reported. In terms of effectiveness, it was difficult to compare the results due to the different doses administered and variables measured, but in general, percentage of wound's size reduction was higher than 80% in wounds, Psoriasis Area and Severity Index and Severity Scoring for Atopic Dermatitis were significantly reduced, for scleroderma, parameters such as Modified Rodnan skin score (MRSC) or European Scleroderma Study Group activity index reported an improvement of the disease and for hypertrophic scars, Vancouver Scar Scale (VSS) score was decreased after applying these therapies. On balance, hMSCs used for the treatment of cutaneous diseases is a promising strategy, however, the different experimental designs and endpoints stablished in each study, makes necessary more research to find the best way to treat each patient and disease.
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Affiliation(s)
- Álvaro Sierra-Sánchez
- Cell Production and Tissue Engineering Unit, Andalusian Network of Design and Translation of Advanced Therapies, Virgen de las Nieves University Hospital, Granada, Spain.,Biosanitary Institute of Granada (ibs.GRANADA), Granada, Spain
| | - Trinidad Montero-Vilchez
- Biosanitary Institute of Granada (ibs.GRANADA), Granada, Spain.,Department of Dermatology, Virgen de las Nieves University Hospital, Granada, Spain
| | - María I Quiñones-Vico
- Cell Production and Tissue Engineering Unit, Andalusian Network of Design and Translation of Advanced Therapies, Virgen de las Nieves University Hospital, Granada, Spain.,Biosanitary Institute of Granada (ibs.GRANADA), Granada, Spain.,Department of Dermatology, Faculty of Medicine, University of Granada, Granada, Spain
| | - Manuel Sanchez-Diaz
- Biosanitary Institute of Granada (ibs.GRANADA), Granada, Spain.,Department of Dermatology, Virgen de las Nieves University Hospital, Granada, Spain
| | - Salvador Arias-Santiago
- Cell Production and Tissue Engineering Unit, Andalusian Network of Design and Translation of Advanced Therapies, Virgen de las Nieves University Hospital, Granada, Spain.,Biosanitary Institute of Granada (ibs.GRANADA), Granada, Spain.,Department of Dermatology, Virgen de las Nieves University Hospital, Granada, Spain.,Department of Dermatology, Faculty of Medicine, University of Granada, Granada, Spain
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Rosa I, Romano E, Fioretto BS, Matucci-Cerinic M, Manetti M. Adipose-derived stem cells: Pathophysiologic implications vs therapeutic potential in systemic sclerosis. World J Stem Cells 2021; 13:30-48. [PMID: 33584978 PMCID: PMC7859990 DOI: 10.4252/wjsc.v13.i1.30] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Revised: 12/04/2020] [Accepted: 12/11/2020] [Indexed: 02/06/2023] Open
Abstract
Adipose-derived stem cells (ADSCs) residing in the stromal vascular fraction (SVF) of white adipose tissue are recently emerging as an alternative tool for stem cell-based therapy in systemic sclerosis (SSc), a complex connective tissue disorder affecting the skin and internal organs with fibrotic and vascular lesions. Several preclinical and clinical studies have reported promising therapeutic effects of fat grafting and autologous SVF/ADSC-based local treatment for facial and hand cutaneous manifestations of SSc patients. However, currently available data indicate that ADSCs may represent a double-edged sword in SSc, as they may exhibit a pro-fibrotic and anti-adipogenic phenotype, possibly behaving as an additional pathogenic source of pro-fibrotic myofibroblasts through the adipocyte-to-myofibroblast transition process. Thus, in the perspective of a larger employ of SSc-ADSCs for further therapeutic applications, it is important to definitely unravel whether these cells present a comparable phenotype and similar immunosuppressive, anti-inflammatory, anti-fibrotic and pro-angiogenic properties in respect to healthy ADSCs. In light of the dual role that ADSCs seem to play in SSc, this review will provide a summary of the most recent insights into the preclinical and clinical studies employing SVF and ADSCs for the treatment of the disease and, at the same time, will focus on the main findings highlighting the possible involvement of these stem cells in SSc-related fibrosis pathogenesis.
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Affiliation(s)
- Irene Rosa
- Department of Experimental and Clinical Medicine, Section of Anatomy and Histology, University of Florence, Florence 50134, Italy
| | - Eloisa Romano
- Department of Experimental and Clinical Medicine, Division of Rheumatology, University of Florence, Florence 50134, Italy
| | - Bianca Saveria Fioretto
- Department of Experimental and Clinical Medicine, Division of Rheumatology, University of Florence, Florence 50134, Italy
| | - Marco Matucci-Cerinic
- Department of Experimental and Clinical Medicine, Division of Rheumatology, University of Florence, Florence 50134, Italy
| | - Mirko Manetti
- Department of Experimental and Clinical Medicine, Section of Anatomy and Histology, University of Florence, Florence 50134, Italy.
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Wang HC, Dong R, Long X, Wang X. Aesthetic and therapeutic outcome of fat grafting for localized Scleroderma treatment: From basic study to clinical application. J Cosmet Dermatol 2021; 20:2723-2728. [PMID: 33486881 DOI: 10.1111/jocd.13941] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2020] [Revised: 12/15/2020] [Accepted: 01/04/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND Localized scleroderma (LoS) is a rare autoimmune disease characterized by skin fibrosis and subcutaneous tissue atrophy, resulting in aesthetic impairment on patients. Fat grafting has been used to treat LoS patients, achieving aesthetic and therapeutic improvement. AIMS This article summarized the epidemiology and pathophysiology of LoS and the current progress and thorny questions of basic and clinical research on fat grafting treating LoS. METHODS The literature of the last 20 years concerning fat grafting of treating LoS was reviewed. RESULTS Fat grafting has been proved to produce aesthetic and therapeutic outcomes on LoS patients, including the improvement of soft tissue atrophy, skin fibrosis and pigmentation. Due to the inflammatory microenvironment of scleroderma, however, fat grafting still faces many difficulties, such as low fat retention. Novel fat grafting methods in order to supplement the deficiency of adipose-derived stem cells and improve fat retention in LoS groups have been proposed whose effectiveness and feasibility is still needed further study. CONCLUSION Currently, fat grafting has been regarded as an effective treatment with a combination of aesthetic and therapeutic outcomes on LoS patients.
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Affiliation(s)
- Hayson Chenyu Wang
- Department of Plastic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.,State Key Laboratory of Complex Severe and Rare Disease, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.,Key Laboratory of Adipose-Derived Stem Cell in Regenerative Medicine, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
| | - Ruijia Dong
- Department of Plastic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.,State Key Laboratory of Complex Severe and Rare Disease, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.,Key Laboratory of Adipose-Derived Stem Cell in Regenerative Medicine, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
| | - Xiao Long
- Department of Plastic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.,State Key Laboratory of Complex Severe and Rare Disease, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.,Key Laboratory of Adipose-Derived Stem Cell in Regenerative Medicine, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
| | - Xiaojun Wang
- Department of Plastic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.,State Key Laboratory of Complex Severe and Rare Disease, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.,Key Laboratory of Adipose-Derived Stem Cell in Regenerative Medicine, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
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30
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An Update on the Potential of Mesenchymal Stem Cell Therapy for Cutaneous Diseases. Stem Cells Int 2021; 2021:8834590. [PMID: 33505474 PMCID: PMC7806381 DOI: 10.1155/2021/8834590] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2020] [Revised: 12/21/2020] [Accepted: 12/25/2020] [Indexed: 12/15/2022] Open
Abstract
Mesenchymal stem or stromal cells (MSCs) are nonhematopoietic postnatal stem cells with self-renewal, multipotent differentiation, and potent immunomodulatory and anti-inflammatory capabilities, thus playing an important role in tissue repair and regeneration. Numerous clinical and preclinical studies have demonstrated the potential application of MSCs in the treatment of tissue inflammation and immune diseases, including inflammatory skin diseases. Therefore, understanding the biological and immunological characteristics of MSCs is important to standardize and optimize MSC-based regenerative therapy. In this review, we highlight the mechanisms underlying MSC-mediated immunomodulation and tissue repair/regeneration and present the latest development of MSC-based clinical trials on cutaneous diseases.
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Abedi M, Alavi-Moghadam S, Payab M, Goodarzi P, Mohamadi-jahani F, Sayahpour FA, Larijani B, Arjmand B. Mesenchymal stem cell as a novel approach to systemic sclerosis; current status and future perspectives. CELL REGENERATION (LONDON, ENGLAND) 2020; 9:20. [PMID: 33258056 PMCID: PMC7704834 DOI: 10.1186/s13619-020-00058-0] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/02/2020] [Accepted: 09/03/2020] [Indexed: 12/13/2022]
Abstract
Systemic sclerosis is a rare chronic autoimmune disease with extensive microvascular injury, damage of endothelial cells, activation of immune responses, and progression of tissue fibrosis in the skin and various internal organs. According to epidemiological data, women's populations are more susceptible to systemic sclerosis than men. Until now, various therapeutic options are employed to manage the symptoms of the disease. Since stem cell-based treatments have developed as a novel approach to rescue from several autoimmune diseases, it seems that stem cells, especially mesenchymal stem cells as a powerful regenerative tool can also be advantageous for systemic sclerosis treatment via their remarkable properties including immunomodulatory and anti-fibrotic effects. Accordingly, we discuss the contemporary status and future perspectives of mesenchymal stem cell transplantation for systemic sclerosis.
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Affiliation(s)
- Mina Abedi
- Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Sepideh Alavi-Moghadam
- Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Moloud Payab
- Metabolomics and Genomics Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Parisa Goodarzi
- Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Fereshteh Mohamadi-jahani
- Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Forough Azam Sayahpour
- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
| | - Bagher Larijani
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical sciences, Tehran, Iran
| | - Babak Arjmand
- Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
- Metabolomics and Genomics Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
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Pignatti M, Spinella A, Cocchiara E, Boscaini G, Lusetti IL, Citriniti G, Lumetti F, Setti G, Dominici M, Salvarani C, De Santis G, Giuggioli D. Autologous Fat Grafting for the Oral and Digital Complications of Systemic Sclerosis: Results of a Prospective Study. Aesthetic Plast Surg 2020; 44:1820-1832. [PMID: 32632623 DOI: 10.1007/s00266-020-01848-2] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2020] [Accepted: 06/14/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND Systemic sclerosis is a connective tissue disease. Skin involvement of the mouth and hand may compromise function and quality of life. Autologous fat grafting has been described as a specific treatment of these clinical features. We report the results of our prospective study designed to treat and prevent skin complications in systemic sclerosis. MATERIALS AND METHODS We treated 25 patients with mouth and/or hand involvement (microstomia, xerostomia, skin sclerosis, Raynaud's phenomenon and long-lasting digital ulcers) with autologous fat grafting, according to the Coleman's technique, around the mouth and/or at the base of each finger. The surgical procedures were repeated in each patient every 6 months for a total of two or three times. Clinical data were collected before the first surgery and again 6 months after each surgical procedure. Pain, skin thickness, saliva production and disability were assessed with validated tests. RESULTS Overall we performed 63 autologous fat grafting sessions (either on the mouth, on the hands or on both anatomical areas). Results at 6 moths after the last session included improvement of xerostomia evaluated with a sialogram, reduction of the skin tension around the mouth and, in the hands, reduction of the Raynaud phenomenon as well as skin thickness. Pain was reduced while the perception of disability improved. Digital ulcers healed completely in 8/9 patients. CONCLUSIONS Our results confirm the efficacy and safety of autologous fat grafting for the treatment of skin complications and digital ulcers due to systemic sclerosis. In addition, the patients' subjective well-being improved. Level of evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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Manetti M. Could autologous adipose-derived stromal vascular fraction turn out an unwanted source of profibrotic myofibroblasts in systemic sclerosis? Ann Rheum Dis 2020; 79:e55. [PMID: 30867149 DOI: 10.1136/annrheumdis-2019-215288] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2019] [Accepted: 03/02/2019] [Indexed: 12/15/2022]
Affiliation(s)
- Mirko Manetti
- Department of Experimental and Clinical Medicine, Section of Anatomy and Histology, University of Florence, Florence I-50134, Italy
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Velier M, Magalon J, Simoncini S, Dignat-George F, Granel B, Paul P, Sabatier F. Response to: 'Could autologous adipose-derived stromal vascular fraction turn out an unwanted source of profibrotic myofibroblasts in systemic sclerosis?' by Manetti. Ann Rheum Dis 2020; 79:e56. [PMID: 30967396 DOI: 10.1136/annrheumdis-2019-215327] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2019] [Accepted: 03/18/2019] [Indexed: 12/26/2022]
Affiliation(s)
- Melanie Velier
- Cell Therapy Department, Hopital de la Conception, Marseille, France
- Cardiovascular and Nutrition Research Center, INSERM, INRA, Aix-Marseille Universite, Marseille, France
| | - Jeremy Magalon
- Cell Therapy Department, Hopital de la Conception, Marseille, France
- Cardiovascular and Nutrition Research Center, INSERM, INRA, Aix-Marseille Universite, Marseille, France
| | - Stephanie Simoncini
- Cardiovascular and Nutrition Research Center, INSERM, INRA, Aix-Marseille Universite, Marseille, France
| | - Françoise Dignat-George
- Cardiovascular and Nutrition Research Center, INSERM, INRA, Aix-Marseille Universite, Marseille, France
| | - Brigitte Granel
- Cardiovascular and Nutrition Research Center, INSERM, INRA, Aix-Marseille Universite, Marseille, France
- Internal Medicine Department, Hopital Nord, Marseille, France
| | - Pascale Paul
- Cell Therapy Department, Hopital de la Conception, Marseille, France
- Cardiovascular and Nutrition Research Center, INSERM, INRA, Aix-Marseille Universite, Marseille, France
| | - Florence Sabatier
- Cell Therapy Department, Hopital de la Conception, Marseille, France
- Cardiovascular and Nutrition Research Center, INSERM, INRA, Aix-Marseille Universite, Marseille, France
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Creadore A, Watchmaker J, Maymone MBC, Pappas L, Lam C, Vashi NA. Cosmetic treatment in patients with autoimmune connective tissue diseases: Best practices for patients with morphea/systemic sclerosis. J Am Acad Dermatol 2020; 83:315-341. [PMID: 32360721 DOI: 10.1016/j.jaad.2019.12.081] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2019] [Revised: 12/24/2019] [Accepted: 12/28/2019] [Indexed: 02/06/2023]
Abstract
Morphea and systemic sclerosis are inflammatory, sclerosing disorders. Morphea primarily affects the dermis and subcutaneous fat, while systemic sclerosis typically involves the skin and internal organs. Functional impairment and cosmetic disfigurement are common in both diseases. Treatment options to mitigate disease progression remain limited. Both functional impairment and cosmetic deficits negatively impact quality of life and psychological well-being in this patient population. While the number of cosmetic procedures performed in the United States continues to rise each year, limited data exist regarding best practices for correcting aesthetic deficits caused by autoimmune conditions. There is scarce information to guide safety decisions regarding laser parameters, soft tissue augmentation, treatment intervals, and the concurrent use of immune-modifying or immune-suppressing medications. Given the fears of disease reactivation and exacerbation from postprocedural inflammation along with limited data, it is difficult for clinicians to provide evidence-based cosmetic treatment with realistic expectations with regard to short- and long-term outcomes. In the first article in this continuing medical education series, we attempt to address this practice gap.
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Affiliation(s)
| | - Jacqueline Watchmaker
- Department of Dermatology, Boston University School of Medicine, Boston, Massachusetts
| | - Mayra B C Maymone
- Department of Dermatology, Boston University School of Medicine, Boston, Massachusetts
| | - Leontios Pappas
- Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts
| | - Christina Lam
- Department of Dermatology, Boston University School of Medicine, Boston, Massachusetts
| | - Neelam A Vashi
- Department of Dermatology, Boston University School of Medicine, Boston, Massachusetts.
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Hsu CC, Cheng JH, Wang CJ, Ko JY, Hsu SL, Hsu TC. Shockwave Therapy Combined with Autologous Adipose-Derived Mesenchymal Stem Cells Is Better than with Human Umbilical Cord Wharton's Jelly-Derived Mesenchymal Stem Cells on Knee Osteoarthritis. Int J Mol Sci 2020; 21:ijms21041217. [PMID: 32059379 PMCID: PMC7072878 DOI: 10.3390/ijms21041217] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2019] [Revised: 02/05/2020] [Accepted: 02/10/2020] [Indexed: 12/15/2022] Open
Abstract
Extracorporeal shockwave therapy (ESWT) and mesenchymal stem cells (MSCs) have been reported to have chondroprotective effects in knee osteoarthritis (OA). Here, we examined whether autologous adipose-derived mesenchymal stem cells (ADMSCs) and human umbilical cord Wharton’s jelly-derived mesenchymal stem cells (WJMSCs) increased the efficacy of ESWT in knee OA, and compared the efficacy of the two. The treatment groups exhibited significant improvement of knee OA according to pathological analysis, micro-computed tomography (CT), and immunohistochemistry (IHC) staining. The ADMSCs and ESWT+ADMSCs groups exhibited increased trabecular thickness and bone volume as compared with the ESWT, WJMSCs, and ESWT+WJMSCs groups individually. According to the results of IHC staining, Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) activity and caspase-3 were significantly reduced in the ADMSCs and ESWT+ADMSCs groups as compared with the WJMSCs and ESWT+WJMSC groups. In mechanistic factor analysis, the synergistic effect of ESWT+ADMSCs was observed as being greater than the efficacies of other treatments in terms of expressions of transforming growth factor (TGF)-β, runt-related transcription factor (RUNX)-2 and sex determining region Y-box (SOX)-9. The type II collagen was expressed at a higher level in the WJMSCs group than in the others. Furthermore, ESWT+ADMSCs reduced the expression of platelet-derived growth factor (PDGF)-BB and increased the expression of bone morphogenetic protein (BMP)-4. Therefore, we demonstrated that ESWT+ADMSCs had a synergistic effect greater than that of ESWT+WJMSCs for the treatment of early knee OA.
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Affiliation(s)
- Chieh-Cheng Hsu
- Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan; (C.-C.H.); (J.-Y.K.); (S.-L.H.); (T.-C.H.)
- Department of Orthopedic Surgery, Sports Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan
| | - Jai-Hong Cheng
- Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan; (C.-C.H.); (J.-Y.K.); (S.-L.H.); (T.-C.H.)
- Medical Research, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan
- Correspondence: (J.-H.C.); (C.-J.W.); Tel.: +886-7-733-6422 (J.-H.C.); +886-7-733-5279 (C.-J.W.)
| | - Ching-Jen Wang
- Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan; (C.-C.H.); (J.-Y.K.); (S.-L.H.); (T.-C.H.)
- Department of Orthopedic Surgery, Sports Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan
- Correspondence: (J.-H.C.); (C.-J.W.); Tel.: +886-7-733-6422 (J.-H.C.); +886-7-733-5279 (C.-J.W.)
| | - Jih-Yang Ko
- Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan; (C.-C.H.); (J.-Y.K.); (S.-L.H.); (T.-C.H.)
- Department of Orthopedic Surgery, Sports Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan
| | - Shan-Ling Hsu
- Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan; (C.-C.H.); (J.-Y.K.); (S.-L.H.); (T.-C.H.)
- Department of Orthopedic Surgery, Sports Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan
- School of Nursing, Fooyin University, Kaohsiung 831, Taiwan
| | - Tsai-Chin Hsu
- Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan; (C.-C.H.); (J.-Y.K.); (S.-L.H.); (T.-C.H.)
- Medical Research, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan
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VELIER M, SIMONCINI S, ABELLAN M, FRANCOIS P, EAP S, LAGRANGE A, BERTRAND B, DAUMAS A, GRANEL B, DELORME B, DIGNAT GEORGE F, MAGALON J, SABATIER F. Adipose-Derived Stem Cells from Systemic Sclerosis Patients Maintain Pro-Angiogenic and Antifibrotic Paracrine Effects In Vitro. J Clin Med 2019; 8:E1979. [PMID: 31739569 PMCID: PMC6912239 DOI: 10.3390/jcm8111979] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2019] [Revised: 11/09/2019] [Accepted: 11/12/2019] [Indexed: 02/06/2023] Open
Abstract
Innovative therapies based on autologous adipose-derived stem/stromal cells (ASC) are currently being evaluated for treatment of systemic sclerosis (SSc). Although paracrine angiogenic and antifibrotic effects are considered the predominant mechanisms of ASC therapeutic potential, the impact of SSc on ASC paracrine functions remains controversial. In this study, phenotype, senescence, differentiation potential, and molecular profile were determined in ASC from SSc patients (SSc-ASC) (n = 7) and healthy donors (HD-ASC) (n = 7). ASC were co-cultured in indirect models with dermal fibroblasts (DF) from SSc patients or endothelial cells to assess their pro-angiogenic and antifibrotic paracrine effects. The angiogenic activity of endothelial cells was measured in vitro using tube formation and spheroid assays. DF collagen and alpha smooth muscle actin (αSMA) content were quantified after five days of co-culture with ASC. Differentiation capacity, senescence, and mRNA profiles did not differ significantly between SSc-ASC and HD-ASC. SSc-ASC retained the ability to stimulate angiogenesis through paracrine mechanisms; however, functional assays revealed reduced potential compared to HD-ASC. DF fibrosis markers were significantly decreased after co-culture with SSc-ASC. Together, these results indicate that SSc effects do not significantly compromise the angiogenic and the antifibrotic paracrine properties of ASC, thereby supporting further development of ASC-based autologous therapies for SSc treatment.
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Affiliation(s)
- Mélanie VELIER
- Aix Marseille University, INSERM, INRA, C2VN, 13005 Marseille, France
- Cell Therapy Department, Hôpital de la Conception, AP-HM, INSERM CIC BT 1409, 13005 Marseille, France
| | | | - Maxime ABELLAN
- Plastic Surgery Department, Hôpital de la Conception, AP-HM, 13005 Marseille, France
| | - Pauline FRANCOIS
- Aix Marseille University, INSERM, INRA, C2VN, 13005 Marseille, France
- Cell Therapy Department, Hôpital de la Conception, AP-HM, INSERM CIC BT 1409, 13005 Marseille, France
| | - Sandy EAP
- R&D Department, Macopharma, 59420 Mouvaux, France
| | | | - Baptiste BERTRAND
- Plastic Surgery Department, Hôpital de la Conception, AP-HM, 13005 Marseille, France
| | - Aurélie DAUMAS
- Aix Marseille University, INSERM, INRA, C2VN, 13005 Marseille, France
- Internal Medicine Department, Hôpital Nord & Hôpital de la Timone, AP-HM, 13005 Marseille, France
| | - Brigitte GRANEL
- Aix Marseille University, INSERM, INRA, C2VN, 13005 Marseille, France
- Internal Medicine Department, Hôpital Nord & Hôpital de la Timone, AP-HM, 13005 Marseille, France
| | | | | | - Jérémy MAGALON
- Aix Marseille University, INSERM, INRA, C2VN, 13005 Marseille, France
- Cell Therapy Department, Hôpital de la Conception, AP-HM, INSERM CIC BT 1409, 13005 Marseille, France
| | - Florence SABATIER
- Aix Marseille University, INSERM, INRA, C2VN, 13005 Marseille, France
- Cell Therapy Department, Hôpital de la Conception, AP-HM, INSERM CIC BT 1409, 13005 Marseille, France
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38
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Daumas A, Magalon J, Delaunay F, Abellan M, Philandrianos C, Sabatier F, Granel B, Magalon G. Fat Grafting for Treatment of Facial Scleroderma. Clin Plast Surg 2019; 47:155-163. [PMID: 31739892 DOI: 10.1016/j.cps.2019.08.016] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
Reparative, angiogenic, and immunomodulatory properties have been attributed to the cells in the adipose tissue-derived stromal vascular fraction. Because of these characteristics, in the last decade, fat grafting for treatment of autoimmune diseases has grown. This article focuses on systemic sclerosis, a rare autoimmune disease characterized by skin fibrosis and microvascular damage. Lesions of the face are almost always present; however, current therapy is insufficient and patients have considerable disability and social discomfort. This article presents our approach to using fat grafting in the face as an innovative and promising therapy for patients with systemic sclerosis.
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Affiliation(s)
- Aurélie Daumas
- Internal Medicine Department, Assistance Publique Hôpitaux de Marseille (AP-HM), Aix-Marseille University, Timone Hospital 264 Rue St Pierre, 13005 Marseille, France
| | - Jeremy Magalon
- Culture and Cell Therapy Laboratory, INSERM CBT-1409, Assistance Publique Hôpitaux de Marseille (AP-HM), Aix-Marseille University, Conception Hospital 147 Bd Baille, 13005 Marseille, France
| | - Flore Delaunay
- Plastic Surgery Department, Centre Hospitalier du Belvédère, 72 rue Louis Pasteur, 76130 Mont Saint Aignan, France; Aix-Marseille University, Marseille, France
| | - Maxime Abellan
- Plastic Surgery Department, Assistance Publique Hôpitaux de Marseille (AP-HM), Aix-Marseille University, Conception Hospital 147 Bd Baille, 13005 Marseille, France
| | - Cécile Philandrianos
- Plastic Surgery Department, Assistance Publique Hôpitaux de Marseille (AP-HM), Aix-Marseille University, Conception Hospital 147 Bd Baille, 13005 Marseille, France
| | - Florence Sabatier
- Culture and Cell Therapy Laboratory, INSERM CBT-1409, Assistance Publique Hôpitaux de Marseille (AP-HM), Aix-Marseille University, Conception Hospital 147 Bd Baille, 13005 Marseille, France
| | - Brigitte Granel
- Internal Medicine Department, Assistance Publique Hôpitaux de Marseille (AP-HM), Aix-Marseille University, Timone Hospital 264 Rue St Pierre, 13005 Marseille, France
| | - Guy Magalon
- Plastic Surgery Department, Assistance Publique Hôpitaux de Marseille (AP-HM), Aix-Marseille University, Conception Hospital 147 Bd Baille, 13005 Marseille, France.
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Scala J, Vojvodic A, Vojvodic P, Vlaskovic-Jovicevic T, Peric-Hajzler Z, Matovic D, Dimitrijevic S, Vojvodic J, Sijan G, Stepic N, Wollina U, Tirant M, Thuong NV, Fioranelli M, Lotti T. Autologous Fat Graft: Not Only an Aesthetic Solution. Open Access Maced J Med Sci 2019; 7:3110-3112. [PMID: 31850099 PMCID: PMC6910800 DOI: 10.3889/oamjms.2019.781] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2019] [Revised: 07/06/2019] [Accepted: 07/07/2019] [Indexed: 12/12/2022] Open
Abstract
Subcutaneous adipose tissue was defined as the “perfect filler” as is soft and malleable and is usually enough present in the body for correcting volume defects and small remodelling purposes. The first attempts to implant autologous adipose tissue dates back to the end of the twentieth century, and with the refinement of harvesting, processing and replanting techniques today a uniform and predictable amount of survival rate were achieved. Those improvements have led to wider use of autologous fat grafts in many medical specialities not only in aesthetic or reconstructive treatments.
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Affiliation(s)
| | - Aleksandra Vojvodic
- Department of Dermatology and Venereology, Military Medical Academy, Belgrade, Serbia
| | - Petar Vojvodic
- Clinic for Psychiatric Disorders "Dr. Laza Lazarevic", Belgrade, Serbia
| | | | | | | | | | - Jovana Vojvodic
- Clinic for Psychiatric Disorders "Dr. Laza Lazarevic", Belgrade, Serbia
| | - Goran Sijan
- Clinic for Plastic Surgery and Burns, Military Medical Academy, Belgrade, Serbia
| | - Nenad Stepic
- Chief of Clinic for Plastic Surgery and Burns, Military Medical Academy, Belgrade, Serbia
| | - Uwe Wollina
- Department of Dermatology and Allergology, Städtisches Klinikum Dresden, Dresden, Germany
| | | | - Nguyen Van Thuong
- Vietnam National Hospital of Dermatology and Venereology, Hanoi, Vietnam
| | - Massimo Fioranelli
- Department of Nuclear Physics, Sub-nuclear and Radiation, G. Marconi University, Rome, Italy
| | - Torello Lotti
- Department of Dermatology, University of G. Marconi, Rome, Italy
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Manetti M, Romano E, Rosa I, Fioretto BS, Praino E, Guiducci S, Iannone F, Ibba-Manneschi L, Matucci-Cerinic M. Systemic Sclerosis Serum Steers the Differentiation of Adipose-Derived Stem Cells Toward Profibrotic Myofibroblasts: Pathophysiologic Implications. J Clin Med 2019; 8:E1256. [PMID: 31430950 PMCID: PMC6723717 DOI: 10.3390/jcm8081256] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2019] [Revised: 08/06/2019] [Accepted: 08/16/2019] [Indexed: 12/16/2022] Open
Abstract
Systemic sclerosis (SSc; scleroderma) is characterized by life-threatening progressive multiorgan fibrosis orchestrated by profibrotic myofibroblasts originating from different sources. Because recent data demonstrated that the majority of myofibroblasts in a murine scleroderma model arise from adipocytic progenitors through the adipocyte-myofibroblast transition process, we sought to determine whether the SSc microenvironment may affect the differentiation potential of adipose-derived stem cells (ADSC). Normal human ADSC from three donors were treated with serum from SSc patients (n = 6), serum from healthy individuals (n = 6), or recombinant human transforming growth factor-β1 (TGFβ1) as positive control of myofibroblastic phenotype induction. ADSC were subjected to in vitro adipogenic differentiation for up to 21 days in the presence of different stimuli followed by lipid content quantification. In selected experiments, adipocytic and mesenchymal/myofibroblast marker gene and protein expression levels were assessed by Real-Time PCR, immunoblotting and immunofluorescence after administration of different stimuli for 72 and 96 h, respectively. Cell contractile phenotype was assayed by collagen gel contraction assay. Likewise stimulation with TGFβ1, SSc serum was able to significantly inhibit the adipocyte differentiation of ADSC as testified by a strong decrease in red-colored lipid droplets after 21 days of adipogenic induction. Treatment of ADSC either with SSc serum or TGFβ1 resulted in the acquisition of a myofibroblast-like phenotype characterized by a reduced expression of the adipocytic markers perilipin and adiponectin, a significant upregulation of the mesenchymal/myofibroblast markers α-SMA+ stress fibers, S100A4 and type I collagen, and an ability to effectively contract collagen gels. In SSc, the pathologic environment may favor the differentiation of ADSC into profibrotic and contractile myofibroblast-like cells. These findings strengthen the notion that the generation of myofibroblasts from ADSC may be relevant in SSc pathophysiology potentially representing a new target for the prevention/treatment of multiorgan fibrosis.
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Affiliation(s)
- Mirko Manetti
- Section of Anatomy and Histology, Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy.
| | - Eloisa Romano
- Division of Rheumatology and Scleroderma Unit, AOUC, Department of Geriatric Medicine, Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy
| | - Irene Rosa
- Section of Anatomy and Histology, Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy
- Division of Rheumatology and Scleroderma Unit, AOUC, Department of Geriatric Medicine, Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy
| | - Bianca Saveria Fioretto
- Division of Rheumatology and Scleroderma Unit, AOUC, Department of Geriatric Medicine, Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy
| | - Emanuela Praino
- Rheumatology Unit, Department of Emergency and Organ Transplantation, University of Bari, 70121 Bari, Italy
| | - Serena Guiducci
- Division of Rheumatology and Scleroderma Unit, AOUC, Department of Geriatric Medicine, Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy
| | - Florenzo Iannone
- Rheumatology Unit, Department of Emergency and Organ Transplantation, University of Bari, 70121 Bari, Italy
| | - Lidia Ibba-Manneschi
- Section of Anatomy and Histology, Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy
| | - Marco Matucci-Cerinic
- Division of Rheumatology and Scleroderma Unit, AOUC, Department of Geriatric Medicine, Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy
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Rozier P, Maria A, Goulabchand R, Jorgensen C, Guilpain P, Noël D. Mesenchymal Stem Cells in Systemic Sclerosis: Allogenic or Autologous Approaches for Therapeutic Use? Front Immunol 2018; 9:2938. [PMID: 30619298 PMCID: PMC6302042 DOI: 10.3389/fimmu.2018.02938] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2018] [Accepted: 11/29/2018] [Indexed: 12/18/2022] Open
Abstract
Systemic sclerosis (SSc) is a rare autoimmune disease, which is potentially lethal. The physiopathology of the disease is still incompletely elucidated although the role of fibroblasts, endothelial cells (ECs), immune cells. and the environment (i.e., oxidative stress) has been demonstrated. This is an intractable disease with an urgent need to provide better therapeutic options to patients. Mesenchymal stem cells (MSCs) represent a promising therapeutic approach thanks to the number of trophic and pleiotropic properties they exert. Among these, MSCs display anti-fibrotic, angiogenic, and immunomodulatory capacities that might be of interest in the treatment of SSc by acting on different processes that are dysregulated in the disease. In the recent years, the therapeutic effectiveness of MSCs has been demonstrated in different preclinical animal models and is being investigated in phase I clinical trials. Both allogenic and autologous transplantation of MSCs isolated from bone marrow or adipose tissue is being evaluated. The rationale for using allogenic MSCs in SSc, as well as in other autoimmune diseases, is based on the possibility that autologous MSCs might be altered in these diseases. In SSc, reports from the literature are controversial. Nevertheless, the role of the oxidative environment and of the crosstalk with neighboring cells (fibroblasts and ECs) on the functional properties of MSCs has been reported. Here, we review the preclinical and clinical data reporting the interest of MSC-based treatment in SSc and question the use of autologous or allogeneic MSCs in perspective of clinical applications.
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Affiliation(s)
- Pauline Rozier
- IRMB, Univ Montpellier, INSERM, CHU Montpellier, Montpellier, France.,Department of Internal Medicine, Multiorganic Diseases, Saint-Eloi Hospital, Montpellier, France
| | - Alexandre Maria
- IRMB, Univ Montpellier, INSERM, CHU Montpellier, Montpellier, France.,Department of Internal Medicine, Multiorganic Diseases, Saint-Eloi Hospital, Montpellier, France
| | - Radjiv Goulabchand
- IRMB, Univ Montpellier, INSERM, CHU Montpellier, Montpellier, France.,Department of Internal Medicine, Multiorganic Diseases, Saint-Eloi Hospital, Montpellier, France
| | - Christian Jorgensen
- IRMB, Univ Montpellier, INSERM, CHU Montpellier, Montpellier, France.,Clinical Immunology and Osteoarticular Diseases Therapeutic Unit, Lapeyronie University Hospital, Montpellier, France
| | - Philippe Guilpain
- IRMB, Univ Montpellier, INSERM, CHU Montpellier, Montpellier, France.,Department of Internal Medicine, Multiorganic Diseases, Saint-Eloi Hospital, Montpellier, France
| | - Danièle Noël
- IRMB, Univ Montpellier, INSERM, CHU Montpellier, Montpellier, France.,Clinical Immunology and Osteoarticular Diseases Therapeutic Unit, Lapeyronie University Hospital, Montpellier, France
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Smith OJ, Jell G, Mosahebi A. The use of fat grafting and platelet-rich plasma for wound healing: A review of the current evidence. Int Wound J 2018; 16:275-285. [PMID: 30460739 DOI: 10.1111/iwj.13029] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2018] [Accepted: 10/16/2018] [Indexed: 12/17/2022] Open
Abstract
Fat grafting is becoming a common procedure in regenerative medicine because of its high content of growth factors and adipose derived stem cells (ADSCs) and the ease of harvest, safety, and low cost. The high concentration of ADSCs found in fat has the potential to differentiate into a wide range of wound-healing cells including fibroblasts and keratinocytes as well as demonstrating proangiogenic qualities. This suggests that fat could play an important role in wound healing. However retention rates of fat grafts are highly variable due in part to inconsistent vascularisation of the transplanted fat. Furthermore, conditions such as diabetes, which have a high prevalence of chronic wounds, reduce the potency and regenerative potential of ADSCs. Platelet-rich plasma (PRP) is an autologous blood product rich in growth factors, cell adhesion molecules, and cytokines. It has been hypothesised that PRP may have a positive effect on the survival and retention of fat grafts because of improved proliferation and differentiations of ADSCs, reduced inflammation, and improved vascularisation. There is also increasing interest in a possible synergistic effect that PRP may have on the healing potential of fat, although the evidence for this is very limited. In this review, we evaluate the evidence in both in vitro and animal studies on the mechanistic relationship between fat and PRP and how this translates to a benefit in wound healing. We also discuss future directions for both research and clinical practice on how to enhance the regenerative potential of the combination of PRP and fat.
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Affiliation(s)
- Oliver J Smith
- Department of Plastic Surgery, Royal Free Hospital, London, UK.,Division of Surgery and Interventional Science, University College London, London, UK
| | - Gavin Jell
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Ash Mosahebi
- Department of Plastic Surgery, Royal Free Hospital, London, UK.,Division of Surgery and Interventional Science, University College London, London, UK
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Autologous Fat Grafting in the Treatment of Facial Scleroderma. Dermatol Res Pract 2018; 2018:6568016. [PMID: 30154838 PMCID: PMC6093005 DOI: 10.1155/2018/6568016] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2018] [Revised: 06/06/2018] [Accepted: 06/28/2018] [Indexed: 12/20/2022] Open
Abstract
Systemic sclerosis (SSc) is a rare systemic autoimmune disease, characterized by progressive cutaneous and internal organ fibrosis. Orofacial manifestations of systemic sclerosis are extremely disabling and treatment options are limited. In this study, we aimed to assess the safety and efficacy of autologous fat grafting in the face of patients with systemic sclerosis. We enrolled 16 SSc patients suffering from facial sclerosis and limited mouth opening capacity. Autologous fat injection ranging from 15 to 40 ml was administered per patient, based on their face morphology. The patients were evaluated at baseline and 3 months after fat injection. Evaluations included mouth opening capacity, mouth handicap in systemic sclerosis (MHISS), Rodnan skin sclerosis score, skin biophysical properties using a sensitive biometrologic device with the assessment of cutaneous resonance running time (CRRT), volumizing and aesthetic effects based on pre- and posttreatment photographs, possible side effects, and global patient satisfaction. Clinical assessment showed autologous fat transfer significantly improved mouth opening capacity and the MHISS and Rodnan score of patients with facial scleroderma (p value <.001). The aesthetic and/or functional results of fat injection were satisfying to about 80% of the patients. The changes in CRRT values were not significant. Our findings support the possible therapeutic role of autologous fat grafting in improving facial scleroderma both in aesthetic and in functional aspects. This trial is registered with IRCT20180209038677N1.
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Didangelos T, Koliakos G, Kouzi K, Arsos G, Kotzampassi K, Tziomalos K, Karamanos D, Hatzitolios AI. Accelerated healing of a diabetic foot ulcer using autologous stromal vascular fraction suspended in platelet-rich plasma. Regen Med 2018; 13:277-281. [PMID: 29715071 DOI: 10.2217/rme-2017-0069] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2017] [Accepted: 02/06/2018] [Indexed: 12/17/2022] Open
Abstract
We describe the case of a Type I diabetic patient with a refractory foot ulcer that remained unhealed for 2 years despite conventional therapy. Autologous adipose-derived stromal vascular fraction suspended in autologous platelet-rich plasma was applied to the wound, which completely healed within 1 month. The wound remained closed with no complications for a 2-year follow-up. Reporting of this and similar cases may lead to larger clinical trials that will prove the efficacy of this therapy that may offer accelerated healing and lessen the financial burden of more expensive therapeutic modalities.
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Affiliation(s)
- Triantafyllos Didangelos
- Diabetes Center, First Propedeutic Department of Internal Medicine, AHEPA Hospital, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - George Koliakos
- Biohellenika Biotechnology SA Georgikis Scholis 65 Thessaloniki, Thessaloniki, Greece
- Laboratory of Biochemistry, AHEPA Hospital, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Kokkona Kouzi
- Biohellenika Biotechnology SA Georgikis Scholis 65 Thessaloniki, Thessaloniki, Greece
- Laboratory of Histology & Embryology, Medical School Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - George Arsos
- Laboratory of Nuclear Medicine, Papageorgiou Hospital, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Katerina Kotzampassi
- First Propaedeutic Department of Surgery, AHEPA Hospital, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Konstantinos Tziomalos
- Diabetes Center, First Propedeutic Department of Internal Medicine, AHEPA Hospital, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Dimitrios Karamanos
- First Department of Surgery, Papageorgiou Hospital, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Apostolos I Hatzitolios
- Diabetes Center, First Propedeutic Department of Internal Medicine, AHEPA Hospital, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece
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