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Arcani R, Velier M, Sabatier F, Simoncini S, Abellan-Lopez M, Granel B, Benyamine A, Gomes de Pinho Q, Dani V, Gentile P, Magalon G, Menkes S, Sampson S, Verpaele A, Vonk L, Magalon J, Daumas A. Nanofat Use in Regenerative Medicine: A Systematic Literature Review and Consensus Recommendations from Expert Opinions. Facial Plast Surg Aesthet Med 2025. [PMID: 40250993 DOI: 10.1089/fpsam.2024.0385] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/20/2025] Open
Abstract
Objective: To report in vitro, preclinical, and clinical effectiveness of nanofat in adults undergoing reconstructive or functional surgery and to produce a series of consensus statements about nanofat definition by experts. Methods: We conducted a systematic review using PubMed and Web of Science database, retaining studies about nanofat alone. To produce consensus recommendations about nanofat, we invited experts to answer a survey about manufacturing, biological characteristics, and nomenclature of nanofat. Results: A review of 39 articles showed that nanofat seems to have strong regenerative potential. There were 16 studies about the clinical effectiveness of the nanofat in wound healing, aesthetic surgery, and functional disabilities. However, majority of applications lack robust clinical evidence, mainly due to the design of the clinical studies. The experts suggested that nanofat refers to lipoaspirate that benefits from a washing step, followed by emulsification (20-30 passes) with a connector size between 1.2 and 1.6 mm, and a final filtration step (pore size around 300-500 µm). Conclusion: Nanofat seems to have strong regenerative potentials but with a lack of robust clinical evidences. Our experts have suggested the first consensus about a definition of the nanofat that can be used by the academic societies in the coming years.
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Affiliation(s)
- Robin Arcani
- Internal Medicine and Therapeutics Department, CHU La Timone, Assistance Publique-Hôpitaux de Marseille (AP-HM), Marseille, France
- Center for Cardiovascular and Nutrition Research (C2VN), INRA 1260, INSERM UMR_S 1263, Aix-Marseille University, Marseille, France
| | - Mélanie Velier
- Center for Cardiovascular and Nutrition Research (C2VN), INRA 1260, INSERM UMR_S 1263, Aix-Marseille University, Marseille, France
- Cell Therapy Department, Hôpital de la Conception, AP-HM, INSERM CIC, Marseille, France
| | - Florence Sabatier
- Center for Cardiovascular and Nutrition Research (C2VN), INRA 1260, INSERM UMR_S 1263, Aix-Marseille University, Marseille, France
- Cell Therapy Department, Hôpital de la Conception, AP-HM, INSERM CIC, Marseille, France
| | - Stéphanie Simoncini
- Center for Cardiovascular and Nutrition Research (C2VN), INRA 1260, INSERM UMR_S 1263, Aix-Marseille University, Marseille, France
| | - Maxime Abellan-Lopez
- Center for Cardiovascular and Nutrition Research (C2VN), INRA 1260, INSERM UMR_S 1263, Aix-Marseille University, Marseille, France
- Plastic Surgery Department, Hôpital de la Conception, AP-HM, Marseille, France
| | - Brigitte Granel
- Center for Cardiovascular and Nutrition Research (C2VN), INRA 1260, INSERM UMR_S 1263, Aix-Marseille University, Marseille, France
- Internal Medicine Department, Hôpital Nord AP-HM, Marseille, France
| | - Audrey Benyamine
- Center for Cardiovascular and Nutrition Research (C2VN), INRA 1260, INSERM UMR_S 1263, Aix-Marseille University, Marseille, France
- Internal Medicine Department, Hôpital Nord AP-HM, Marseille, France
| | - Quentin Gomes de Pinho
- Center for Cardiovascular and Nutrition Research (C2VN), INRA 1260, INSERM UMR_S 1263, Aix-Marseille University, Marseille, France
- Internal Medicine Department, Hôpital Nord AP-HM, Marseille, France
| | | | - Pietro Gentile
- Department of Surgical Science, Medical School, "Tor Vergata" University, Rome, Italy
| | | | | | - Steve Sampson
- The Orthohealing Center, Los Angeles, California, USA
| | - Alexis Verpaele
- Tonnard and Verpaele Plastic Surgery Associates, Ghent, Belgium
| | - Lucienne Vonk
- Department of Orthopaedics, University Medical Center Utrecht, Utrecht, The Netherlands & Xintela AB, Lund, Sweden
| | - Jérémy Magalon
- Center for Cardiovascular and Nutrition Research (C2VN), INRA 1260, INSERM UMR_S 1263, Aix-Marseille University, Marseille, France
- Cell Therapy Department, Hôpital de la Conception, AP-HM, INSERM CIC, Marseille, France
| | - Aurélie Daumas
- Internal Medicine and Therapeutics Department, CHU La Timone, Assistance Publique-Hôpitaux de Marseille (AP-HM), Marseille, France
- Center for Cardiovascular and Nutrition Research (C2VN), INRA 1260, INSERM UMR_S 1263, Aix-Marseille University, Marseille, France
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Behn A, Brendle S, Ehrnsperger M, Zborilova M, Grupp TM, Grifka J, Schäfer N, Grässel S. Filtered and unfiltered lipoaspirates reveal novel molecular insights and therapeutic potential for osteoarthritis treatment: a preclinical in vitro study. Front Cell Dev Biol 2025; 13:1534281. [PMID: 40083666 PMCID: PMC11903472 DOI: 10.3389/fcell.2025.1534281] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Accepted: 02/05/2025] [Indexed: 03/16/2025] Open
Abstract
Introduction Orthobiologics, such as autologous nanofat, are emerging as a potential treatment option for osteoarthritis (OA), a common degenerative joint causing pain and disability in the elderly. Nanofat, a minimally processed human fat graft rich in stromal vascular fraction (SVF) secretory factors, has shown promise in relieving pain. This study aimed to elucidate the molecular mechanisms underlying nanofat treatment of OA-affected cells and compare two filtration systems used for nanofat preparation. Methods Chondrocytes and synoviocytes were isolated from articular cartilage and synovium of 22 OA-patients. Lipoaspirates from 13 OA-patients were emulsified using the Adinizer® or Lipocube™ Nano filter systems to generate nanofat. The fluid phase of SVF from both filtered and unfiltered lipoaspirates was applied to OA-affected cells. Luminex multiplex ELISA were performed with lipoaspirates and cell supernatants alongside functional assays evaluating cell migration, proliferation, metabolic activity, and senescence. Results A total of 62 cytokines, chemokines, growth factors, neuropeptides, matrix-degrading enzymes, and complement components were identified in lipoaspirates. Among these, significant concentration differences were observed for TIMP-2, TGF-ß3, and complement component C3 between the filtered and unfiltered samples. Nanofat enhanced chondrocyte proliferation and migration, as well as synoviocyte migration and metabolic activity, while reducing chondrocyte metabolic activity. Pain-related factors like β-NGF, MCP-1, Substance P, VEGF, and αCGRP were reduced, while anti-inflammatory TGF-β1+3 increased and pro-inflammatory cytokines (IL-5, IL-7, IL-15, and IFN-γ) decreased. Nanofat also elevated secretion of complement components and TIMPs in both cell types. Notably, our results revealed no significant differences in cellular effects between sSVF filtered using the Adinizer® and Lipocube™ Nano systems, as well as compared to unfiltered sSVF. Discussion Here, we provide first insights into how autologous nanofat therapy may ameliorate OA by enhancing chondrocyte proliferation and synoviocyte migration while modulating inflammatory and pain-related factors. However, further research is needed to determine its effects on cartilage regeneration.
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Affiliation(s)
- Alissa Behn
- Department of Orthopaedic Surgery, Experimental Orthopaedics, Centre for Medical Biotechnology (ZMB/Biopark 1), University of Regensburg, Regensburg, Germany
| | - Saskia Brendle
- Research and Development, Aesculap AG, Tuttlingen, Germany
- Department of Orthopaedic and Trauma Surgery, Musculoskeletal University Center Munich (MUM), LMU Munich, Munich, Germany
| | - Marianne Ehrnsperger
- Department of Orthopedic Surgery, University of Regensburg, Asklepios, Germany
- Department of Trauma Surgery, University Medical Center Regensburg, Regensburg, Germany
| | - Magdalena Zborilova
- Department of Orthopedic Surgery, University of Regensburg, Asklepios, Germany
| | - Thomas M. Grupp
- Research and Development, Aesculap AG, Tuttlingen, Germany
- Department of Orthopaedic and Trauma Surgery, Musculoskeletal University Center Munich (MUM), LMU Munich, Munich, Germany
| | - Joachim Grifka
- Department of Orthopedic Surgery, University of Regensburg, Asklepios, Germany
- Department of Orthopedics and Ergonomics, Ostbayerische Technische Hochschule (OTH), Regensburg, Germany
| | - Nicole Schäfer
- Department of Orthopaedic Surgery, Experimental Orthopaedics, Centre for Medical Biotechnology (ZMB/Biopark 1), University of Regensburg, Regensburg, Germany
| | - Susanne Grässel
- Department of Orthopaedic Surgery, Experimental Orthopaedics, Centre for Medical Biotechnology (ZMB/Biopark 1), University of Regensburg, Regensburg, Germany
- Department of Orthopedic Surgery, University of Regensburg, Asklepios, Germany
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Jeyaraman N, Shrivastava S, Ravi VR, Nallakumarasamy A, Jeyaraman M. Current status of nanofat in the management of knee osteoarthritis: A systematic review. World J Orthop 2025; 16:99690. [PMID: 39850037 PMCID: PMC11752481 DOI: 10.5312/wjo.v16.i1.99690] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2024] [Revised: 12/07/2024] [Accepted: 12/25/2024] [Indexed: 01/13/2025] Open
Abstract
BACKGROUND Osteoarthritis (OA) is a prevalent joint disorder requiring innovative treatment approaches. AIM To evaluate the use of nanofat, a specialized form of adipose tissue-derived cells, in the treatment of OA, by examining its efficacy, safety profile, mechanisms of action, comparative effectiveness, and long-term outcomes. METHODS A comprehensive review of preclinical studies, clinical trials, and in vitro investigations was conducted. The included studies provided insights into the potential role of nanofat in OA treatment, addressing its efficacy, safety profile, mechanisms of action, comparative effectiveness, and long-term outcomes. RESULTS Clinical studies consistently reported the efficacy of nanofat in providing pain relief and functional improvement in patients with OA. Local adverse events were limited to the injection site, such as localized pain and inflammation, and resolved within a few days to weeks. Systemic adverse events were rare, and no significant long-term complications were observed. Mechanistically, nanofat was found to enhance chondrocyte proliferation, reduce inflammation, and promote angiogenesis, thereby contributing to its therapeutic effects. CONCLUSION Nanofat therapy holds promise as a therapeutic option for managing OA, providing pain relief, functional improvement, and potential tissue regeneration. The safety profile of nanofat treatment appears favorable, but long-term data are still limited. Standardized protocols, larger randomized controlled trials, longer follow-up periods, and cost-effectiveness evaluations are warranted to establish optimal protocols, comparative effectiveness, and long-term outcomes. Despite current limitations, nanofat therapy demonstrates translational potential and should be considered in clinical practice for OA treatment, with careful patient selection and monitoring.
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Affiliation(s)
- Naveen Jeyaraman
- Department of Orthopaedics, Datta Meghe Institute of Higher Education and Research, Wardha 442004, Maharashtra, India
- Department of Regenerative Medicine, Mother Cell Regenerative Centre, Tiruchirappalli 620017, Tamil Nadu, India
| | - Sandeep Shrivastava
- Department of Orthopaedics, Datta Meghe Institute of Higher Education and Research, Wardha 442004, Maharashtra, India
| | - VR Ravi
- Department of Regenerative Medicine, Mother Cell Regenerative Centre, Tiruchirappalli 620017, Tamil Nadu, India
| | - Arulkumar Nallakumarasamy
- Department of Orthopaedics, Datta Meghe Institute of Higher Education and Research, Wardha 442004, Maharashtra, India
- Department of Regenerative Medicine, Mother Cell Regenerative Centre, Tiruchirappalli 620017, Tamil Nadu, India
| | - Madhan Jeyaraman
- Department of Regenerative Medicine, Mother Cell Regenerative Centre, Tiruchirappalli 620017, Tamil Nadu, India
- Department of Orthopaedics, ACS Medical College and Hospital, Dr MGR Educational and Research Institute, Chennai 600077, Tamil Nadu, India
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Hekimoglu ER, Esrefoglu M, Cimen FBK, Pasin Ö, Dedeakayogullari H. Therapeutic Potential of Stromal Vascular Fraction in Enhancing Wound Healing: A Preclinical Study. Aesthetic Plast Surg 2024:10.1007/s00266-024-04554-5. [PMID: 39681692 DOI: 10.1007/s00266-024-04554-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2024] [Accepted: 11/11/2024] [Indexed: 12/18/2024]
Abstract
BACKGROUND Adipose tissue provides an abundant source of stromal vascular fraction (SVF) cells for immediate administration. It can also give rise to many multipotent adipose-derived stromal cells. SVF is the population of cells obtained from mechanical or enzymatic digestion of lipoaspirate with no necessity for cell culture or expansion. Recently, the heterogeneous cell population found in the SVF gained wide-ranging translational significance in regenerative medicine. METHODS Forty-eight male rats were randomly divided into two main groups, including the control and SVF groups. Each group was further divided into four groups as follows: 0th-, 3rd-, 7th-, and 10th-day groups. A skin excision of 1 × 1 cm covering the epidermis and dermis was performed on the back skin. Just after the wound was created, a subepidermal injection of SVF was applied. SVF was obtained from human adipose tissue using Lipocube SVFTM. On the 0th (1 h after the injections), 3rd, 7th, and 10th days, rats were killed, and skin excisions from the wound areas tissues were performed. Histopathological, biochemical, and western blotting analyses were performed on tissues. RESULTS Our data showed that SVF obtained from a healthy woman improved wound healing in healthy rats. SVF has promoted wound healing mainly because of its antioxidant, antiapoptotic, and fibroblast/myofibroblast stimulating effects. SVF stimulated collagen production and contraction of the wound lips, supporting the closure. CONCLUSIONS Our study provides additional data about the efficacy and pathophysiological and molecular mechanisms of the action of SVF on wound healing in healthy subjects. Our study is an experimental animal study. NO LEVEL ASSIGNED This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.
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Affiliation(s)
- Emine Rumeysa Hekimoglu
- Department of Histology and Embryology, Faculty of Medicine, Bezmialem Vakıf University, Fatih, Istanbul, Turkey.
| | - Mukaddes Esrefoglu
- Department of Histology and Embryology, Faculty of Medicine, Bezmialem Vakıf University, Fatih, Istanbul, Turkey
| | - Fatma Bedia Karakaya Cimen
- Department of Histology and Embryology, Faculty of Medicine, Bezmialem Vakıf University, Fatih, Istanbul, Turkey
| | - Özge Pasin
- Department of Biostatistics, Faculty of Medicine, Bezmialem Vakif University, Istanbul, Turkey
| | - Huri Dedeakayogullari
- Department of Medical Biochemistry, Faculty of Medicine, Istinye University, Istanbul, Turkey
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Ventura C, Bondioli E, de Vita R, Rigotti G, Morigi F, Scarpellini F, Di Fede F, Nanni-Costa A, Melandri D. Autologous Cryopreserved Adipose Tissue Using an Innovative Technique: An In Vitro Biological Characterization. Aesthet Surg J 2024; 45:NP16-NP24. [PMID: 39302643 DOI: 10.1093/asj/sjae192] [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: 06/07/2024] [Revised: 08/23/2024] [Accepted: 09/18/2024] [Indexed: 09/22/2024] Open
Abstract
BACKGROUND Utilization of autologous adipose tissue transplantation in plastic and orthopedic surgery such as breast reconstruction and intra-articular injection has become an attractive surgical treatment with satisfactory clinical outcomes. Nevertheless, repeated liposuctions necessary to harvest fatty tissue, normally performed with sedation or general anesthesia, may represent a noteworthy concern. OBJECTIVES The aim of this study was to demonstrate through an in vitro characterization the validity of the surgical option of cryopreserved autologous adipose tissue harvested in a single shot for repeated graft transfer in breast reconstruction without impairment of cell viability and sterility. METHODS Adipose tissue was collected by standard liposuction from patients who needed numerous fat grafting procedures for breast reconstruction. According to an innovative and patented cryopreservation method, autologous adipose tissue was subsequently fractioned in a sterile bag system and frozen at the RER Tissue Bank of the Emilia Romagna Region. Each graft was evaluated for sterility and cell viability immediately after harvesting, and 1, 3, 6, 12, and preliminarily 18 months after cryopreservation and thawing. RESULTS In vitro results showed that after processing, middle-term and long-term cryopreservation, and subsequent thawing, autologous cryopreserved adipose tissue retained absence of bacterial contamination, high cellular viability, and unmodified histomorphological properties, thereby ensuring maintenance of the stromal vascular niche and the filling properties in different multistep surgical procedures. CONCLUSIONS In vitro study and sterility assessment showed that autologous cryopreserved adipose tissue grafting is a safe procedure, making it possible to avoid multiple liposuction surgery. No impairment of sterility, cell viability, or morphology was observed over time.
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You X, Gao J, Yao Y. Advanced methods to mechanically isolate stromal vascular fraction: A concise review. Regen Ther 2024; 27:120-125. [PMID: 38571891 PMCID: PMC10987671 DOI: 10.1016/j.reth.2024.03.020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2023] [Revised: 02/29/2024] [Accepted: 03/17/2024] [Indexed: 04/05/2024] Open
Abstract
Adipose tissue is a highly attractive reservoir of stem cells due to its accessibility and abundance, and the SVF within it holds great promise for stem cell-based therapies. The use of mechanical methods for SVF isolation from adipose tissue is preferred over enzymatic methods, as it can be readily applied in clinical settings without additional processing steps. However, there is a lack of consensus on the optimal approach for mechanically isolating SVF. This comprehensive review aims to present and compare the latest mechanical isolation methods for SVF from adipose tissue, including centrifugation, filtration/washing, emulsification, vibration, and mincing/adiponizing. Each of these methods possesses unique advantages and limitations, and yet, no conclusive evidence has emerged demonstrating the superiority of one approach over the others, primarily due to the dearth of well-controlled prospective studies in this field.
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Affiliation(s)
- Xin You
- Department of Plastic and Cosmetic Surgery, Nanfang Hospital, Southern Medical University, 1838 Guangzhou North Road, Guangzhou, Guangdong 510515, PR China
| | - JianHua Gao
- Department of Plastic and Cosmetic Surgery, Nanfang Hospital, Southern Medical University, 1838 Guangzhou North Road, Guangzhou, Guangdong 510515, PR China
| | - Yao Yao
- Department of Plastic and Cosmetic Surgery, Nanfang Hospital, Southern Medical University, 1838 Guangzhou North Road, Guangzhou, Guangdong 510515, PR China
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Bonomi F, Limido E, Weinzierl A, Ampofo E, Harder Y, Menger MD, Laschke MW. Nanofat Improves Vascularization and Tissue Integration of Dermal Substitutes without Affecting Their Biocompatibility. J Funct Biomater 2024; 15:294. [PMID: 39452592 PMCID: PMC11508499 DOI: 10.3390/jfb15100294] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2024] [Revised: 09/29/2024] [Accepted: 10/01/2024] [Indexed: 10/26/2024] Open
Abstract
Dermal substitutes require sufficient tissue integration and vascularization to be successfully covered with split-thickness skin grafts. To rapidly achieve this, we provide the proof of principle for a novel vascularization strategy with high translational potential. Nanofat was generated from subcutaneous adipose tissue of green fluorescence protein (GFP)+ C57BL/6J donor mice and seeded onto small samples (4 mm in diameter) of the clinically approved dermal substitute Integra®. These samples and non-seeded controls were then implanted into full-thickness skin defects in the dorsal skinfold chamber of C57BL/6J wild-type mice and analyzed by intravital fluorescence microscopy, histology and immunohistochemistry over a 14-day period. Nanofat-seeded dermal substitutes exhibited an accelerated vascularization, as indicated by a significantly higher functional microvessel density on days 10 and 14 when compared to controls. This was primarily caused by the reassembly of GFP+ microvascular fragments inside the nanofat into microvascular networks. The improved vascularization promoted integration of the implants into the surrounding host tissue, which finally exhibited an increased formation of a collagen-rich granulation tissue. There were no marked differences in the inflammatory host tissue reaction to nanofat-seeded and control implants. These findings demonstrate that nanofat significantly improves the in vivo performance of dermal substitutes without affecting their biocompatibility.
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Affiliation(s)
- Francesca Bonomi
- Institute for Clinical and Experimental Surgery, Saarland University, 66421 Homburg, Germany; (F.B.); (E.L.); (A.W.); (E.A.); (M.D.M.)
| | - Ettore Limido
- Institute for Clinical and Experimental Surgery, Saarland University, 66421 Homburg, Germany; (F.B.); (E.L.); (A.W.); (E.A.); (M.D.M.)
- Department of Surgery, Ospedale Beata Vergine Mendrisio, Ente Ospedaliero Cantonale (EOC), 6850 Mendrisio, Switzerland
| | - Andrea Weinzierl
- Institute for Clinical and Experimental Surgery, Saarland University, 66421 Homburg, Germany; (F.B.); (E.L.); (A.W.); (E.A.); (M.D.M.)
- Department of Plastic Surgery and Hand Surgery, University Hospital Zurich, 8006 Zurich, Switzerland
| | - Emmanuel Ampofo
- Institute for Clinical and Experimental Surgery, Saarland University, 66421 Homburg, Germany; (F.B.); (E.L.); (A.W.); (E.A.); (M.D.M.)
| | - Yves Harder
- Department of Plastic, Reconstructive and Aesthetic Surgery and Hand Surgery, Centre Hospitalier Universitaire Vaudois (CHUV), 1005 Lausanne, Switzerland;
- Faculty of Biology and Medicine, University of Lausanne (UNIL), 1005 Lausanne, Switzerland
| | - Michael D. Menger
- Institute for Clinical and Experimental Surgery, Saarland University, 66421 Homburg, Germany; (F.B.); (E.L.); (A.W.); (E.A.); (M.D.M.)
| | - Matthias W. Laschke
- Institute for Clinical and Experimental Surgery, Saarland University, 66421 Homburg, Germany; (F.B.); (E.L.); (A.W.); (E.A.); (M.D.M.)
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Tran VVT, Jin X, Hong KY, Chang H. Effects of Nanofat in Plastic and Reconstructive Surgery: A Systematic Review. Plast Reconstr Surg 2024; 154:451e-464e. [PMID: 37400953 DOI: 10.1097/prs.0000000000010905] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/05/2023]
Abstract
BACKGROUND Since nanofat was first introduced by Tonnard in 2013, numerous studies have reported positive findings with its use; however, concerns exist regarding its effects and mechanisms, and the various methods used to generate nanofat also remain unclear. The authors conducted a systematic review to evaluate the efficacy of nanofat grafting alone in plastic and reconstructive surgery. METHODS The MEDLINE, Embase, Cochrane Central, Web of Science, and Scopus databases were searched for studies related to the use of nanofat grafting alone in plastic and reconstructive surgery. Outcomes of interest were all clinical results in humans or animals. RESULTS Twelve studies were included. No meta-analysis was conducted due to the clinical heterogeneity of the studies. In general, included studies had a low level of evidence. Six studies ( n = 253 patients) showed significant improvements in scar characteristics based on Patient and Observer Scar Assessment Scale, FACE-Q scale, physician assessment, patient satisfaction, and Vancouver Scar Scale scores. Four studies described the benefits of nanofat in skin rejuvenation (wrinkles, fine rhytides, pigmentation, and discoloration) through photographs, questionnaires, and indentation indices. Histologic evaluation illustrated overall increases in skin thickness, collagen, and elastic fibers. Three experimental studies showed the beneficial effects of nanofat on fat grafting, diabetic wound healing, and hair growth, with compelling histological evidence. No severe complication was reported. CONCLUSIONS Nanofat grafting shows potential benefits in scar and antiaging treatments, with conclusive histological evidence. Clinical studies of fat grafting, wound healing, and hair growth should be conducted, based on the results of this systematic review. Nanofat grafting could be a practical and safe procedure.
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Affiliation(s)
- Vinh Vuong The Tran
- From the Hi-Tech Center, Vinmec Healthcare System
- Department of Plastic and Reconstructive Surgery, Seoul National University College of Medicine
| | - Xian Jin
- Department of Plastic and Reconstructive Surgery, Seoul National University College of Medicine
| | - Ki Yong Hong
- Department of Plastic and Reconstructive Surgery, Seoul National University Hospital, Seoul National University College of Medicine
| | - Hak Chang
- Department of Plastic and Reconstructive Surgery, Seoul National University Hospital, Seoul National University College of Medicine
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Ramaut L, Moonen L, Geeroms M, Leemans G, Peters E, Forsyth R, Gutermuth J, Hamdi M. Improvement in Early Scar Maturation by Nanofat Infiltration: Histological and Spectrophotometric Preliminary Results From a Split Scar-Controlled, Randomized, Double-Blinded Clinical Trial. Aesthet Surg J Open Forum 2024; 6:ojae072. [PMID: 39360238 PMCID: PMC11446608 DOI: 10.1093/asjof/ojae072] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/04/2024] Open
Abstract
Background The regenerative properties of stromal vascular fraction (SVF) in wound healing and scar formation are a subject of increasing clinical interest. Objectives Although preclinical studies have confirmed the angiogenetic, proliferative, and antifibrotic properties of SVF, there is limited clinical evidence from randomized controlled clinical trials. Methods Twelve patients who underwent abdominoplasty were included in this clinical study. Nanofat was mechanically obtained intraoperatively and infiltrated intradermally in the sutured surgical wound, randomly assigned to either the left or the right side. The abdominal scar was evaluated with the Patient and Observer Scar Assessment Scale, whereas erythema and pigmentation were measured with a reflectance spectrophotometry device (Mexameter, Courage + Khazaka electronic GmbH, Köln,Germany). Histological analysis and electron scan microscopy of tissue biopsies were performed at 8 months. Results The treated side of the scar showed significantly less erythema at 3- and 6-month follow-ups, but this difference reduced after 12 months. Patients reported better scar scores at the 6-month follow-up with a significantly better color at the treated side. Observers reported better overall scar scores at the treated side at 3-, 6-, and 12-month follow-ups, with better vascularization, pigmentation, and thickness. There was no statistically significant difference in terms of histological analysis between the 2 groups. There was no difference in the occurrence of adverse events between both sides. Conclusions Infiltration of nanofat exhibited promising results in surgical scar maturation characterized by less erythema and better texture. More clinical trials with a larger sample size are warranted to better elucidate the possible benefits of SVF on surgical scar formation. Level of Evidence 5
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Sowa Y, Sawai S, Yamamoto K, Sunaga A, Saito N, Shirado T, Toyohara Y, Bolun L, Yoshimura K, Mazda O. Micronized cellular adipose matrix purified with a bladed connector contains abundant functional adipose stem cells. Tissue Cell 2024; 89:102457. [PMID: 38996772 DOI: 10.1016/j.tice.2024.102457] [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: 02/06/2024] [Revised: 06/23/2024] [Accepted: 06/24/2024] [Indexed: 07/14/2024]
Abstract
INTRODUCTION A specialized device equipped with a sharp blade filter has been developed to enable more efficient purification of a micronized cellular adipose matrix (MCAM) containing stem cells. The aim of this study is to compare the characteristics and functions of the population of stromal cells (mSVF) and cultured cells (mASCs) purified using this device with those of cSVF and cASCs obtained through conventional enzymatic purification. METHODS Cell viability, proliferation capacity and yield were assessed. Characterization of stem cell potency was performed by analyzing cell surface markers including CD34, a marker of activated adipose-derived stem cells. The trilineage differentiation potential was evaluated using RT-PCR and histology. RESULTS The yield rate of mSVF obtained from MCAM was significantly higher than that with the conventional method, although use of the device resulted in a slight decrease in cell viability. After culture, mASCs exhibited a remarkable clonogenic potential and significantly higher cell proliferation potential than cASCs. The mASCs also displayed a distinct pattern of ASC cell surface markers, increased expression of genes related to CD34, high pluripotency, and a high trilineage differentiation ability. CONCLUSION The specialized device enhanced the yield of SVF and produced cells with high proliferation rates and characteristics that include expression of stem cell markers.
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Affiliation(s)
- Yoshihiro Sowa
- Department of Plastic Surgery, Jichi Medical University, Japan; Department of Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Plastic and Reconstructive Surgery, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
| | - Seiji Sawai
- Department of Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Kenta Yamamoto
- Department of Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Ataru Sunaga
- Department of Plastic Surgery, Jichi Medical University, Japan
| | - Natsumi Saito
- Department of Plastic Surgery, Jichi Medical University, Japan
| | - Takako Shirado
- Department of Plastic Surgery, Jichi Medical University, Japan
| | | | - Li Bolun
- Department of Plastic Surgery, Jichi Medical University, Japan
| | | | - Osam Mazda
- Department of Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
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11
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Mundluru VK, Naidu MJ, Mundluru RT, Jeyaraman N, Muthu S, Ramasubramanian S, Jeyaraman M. Non-enzymatic methods for isolation of stromal vascular fraction and adipose-derived stem cells: A systematic review. World J Methodol 2024; 14:94562. [PMID: 38983657 PMCID: PMC11229868 DOI: 10.5662/wjm.v14.i2.94562] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2024] [Revised: 05/03/2024] [Accepted: 05/30/2024] [Indexed: 06/13/2024] Open
Abstract
BACKGROUND Adipose-derived stem cells (ADSCs) and the stromal vascular fraction (SVF) have garnered substantial interest in regenerative medicine due to their potential to treat a wide range of conditions. Traditional enzymatic methods for isolating these cells face challenges such as high costs, lengthy processing time, and regu-latory complexities. AIM This systematic review aimed to assess the efficacy and practicality of non-enzymatic, mechanical methods for isolating SVF and ADSCs, comparing these to conventional enzymatic approaches. METHODS Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a comprehensive literature search was conducted across multiple databases. Studies were selected based on inclusion criteria focused on non-enzymatic isolation methods for SVF and ADSCs from adipose tissue. The risk of bias was assessed, and a qualitative synthesis of findings was performed due to the methodological heterogeneity of the included studies. RESULTS Nineteen studies met the inclusion criteria, highlighting various mechanical techniques such as centrifugation, vortexing, and ultrasonic cavitation. The review identified significant variability in cell yield and viability, and the integrity of isolated cells across different non-enzymatic methods compared to enzymatic procedures. Despite some advantages of mechanical methods, including reduced processing time and avoidance of enzymatic reagents, the evidence suggests a need for optimization to match the cell quality and therapeutic efficacy achievable with enzymatic isolation. CONCLUSION Non-enzymatic, mechanical methods offer a promising alternative to enzymatic isolation of SVF and ADSCs, potentially simplifying the isolation process and reducing regulatory hurdles. However, further research is necessary to standardize these techniques and ensure consistent, high-quality cell yields for clinical applications. The development of efficient, safe, and reproducible non-enzymatic isolation methods could significantly advance the field of regenerative medicine.
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Affiliation(s)
- Vamsi Krishna Mundluru
- Department of Orthopaedics, MJ Naidu Super Speciality Hospital, Vijayawada 520002, Andhra Pradesh, India
- Department of Regenerative Medicine, StemC Clinics, Vijayawada 520002, Andhra Pradesh, India
| | - MJ Naidu
- Department of Orthopaedics, MJ Naidu Super Speciality Hospital, Vijayawada 520002, Andhra Pradesh, India
- Department of Regenerative Medicine, StemC Clinics, Vijayawada 520002, Andhra Pradesh, India
| | - Ravi Teja Mundluru
- Department of Orthopaedics, MJ Naidu Super Speciality Hospital, Vijayawada 520002, Andhra Pradesh, India
- Department of Regenerative Medicine, StemC Clinics, Vijayawada 520002, Andhra Pradesh, India
| | - Naveen Jeyaraman
- Department of Regenerative Medicine, StemC Clinics, Vijayawada 520002, Andhra Pradesh, India
- Department of Orthopaedics, ACS Medical College and Hospital, Dr. MGR Educational and Research Institute, Chennai 600077, Tamil Nadu, India
- Department of Orthopaedics, Orthopaedic Research Group, Coimbatore 641045, Tamil Nadu, India
| | - Sathish Muthu
- Department of Orthopaedics, Orthopaedic Research Group, Coimbatore 641045, Tamil Nadu, India
- Department of Orthopaedics, Government Medical College and Hospital, Karur 639004, Tamil Nadu, India
- Department of Biotechnology, Faculty of Engineering, Karpagam Academy of Higher Education, Coimbatore 641021, Tamil Nadu, India
| | - Swaminathan Ramasubramanian
- Department of Orthopaedics, Government Medical College, Omandurar Government Estate, Chennai 600002, Tamil Nadu, India
| | - Madhan Jeyaraman
- Department of Regenerative Medicine, StemC Clinics, Vijayawada 520002, Andhra Pradesh, India
- Department of Orthopaedics, ACS Medical College and Hospital, Dr. MGR Educational and Research Institute, Chennai 600077, Tamil Nadu, India
- Department of Orthopaedics, Orthopaedic Research Group, Coimbatore 641045, Tamil Nadu, India
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12
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Malisetyan T, Harrison JL, Shahriari SR, Clarke TN, Rogol EV, Borah GL. Autologous Fat Transfer in Craniofacial Surgery. FACE 2024; 5:279-291. [DOI: 10.1177/27325016241238441] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
Abstract
Over the past two decades, autologous fat transfer has garnered significant recognition and widespread adoption within esthetic and reconstructive surgical domains. In craniofacial surgery, fat transplantation is frequently employed to address soft tissue volumetric deficiencies and asymmetries that influence facial contours. While adipose tissue (AT) is widely regarded as an optimal choice for augmentation due to its abundant availability and biocompatibility, the unpredictability and heightened resorption rates observed with traditional lipofilling techniques present a challenge for clinicians. Adipose-derived stem cells (ASCs) housed within the grafted tissue play a pivotal role in graft survival and offer avenues for tissue repair due to their angiogenic, anti-inflammatory, and immunosuppressive properties. Micro Fragmentation of Adipose Tissue (MFAT), utilized in several FDA-approved processing devices, has demonstrated promising outcomes in treating osteoarthritic joints, with success primarily attributed to enhanced paracrine function of ASCs via preservation of the perivascular niche. Currently, its application for treating bone or articular defects in the craniofacial region, including abnormalities of the temporomandibular joint, remains limited. This scarcity underscores the need for further investigation prior to its widespread integration into clinical practice.
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Affiliation(s)
- Tatevik Malisetyan
- Nova Southeastern University, Dr. Kiran C. Patel College of Allopathic Medicine, Fort Lauderdale, FL, USA
| | | | | | - Tegan N. Clarke
- University of New Mexico School of Medicine, Albuquerque, NM, USA
| | | | - Gregory L. Borah
- University of New Mexico School of Medicine, Albuquerque, NM, USA
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13
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Goncharov EN, Koval OA, Igorevich EI, Encarnacion Ramirez MDJ, Nurmukhametov R, Valentinovich KK, Montemurro N. Analyzing the Clinical Potential of Stromal Vascular Fraction: A Comprehensive Literature Review. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:221. [PMID: 38399509 PMCID: PMC10890435 DOI: 10.3390/medicina60020221] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/12/2023] [Revised: 01/11/2024] [Accepted: 01/25/2024] [Indexed: 02/25/2024]
Abstract
Background: Regenerative medicine is evolving with discoveries like the stromal vascular fraction (SVF), a diverse cell group from adipose tissue with therapeutic promise. Originating from fat cell metabolism studies in the 1960s, SVF's versatility was recognized after demonstrating multipotency. Comprising of cells like pericytes, smooth muscle cells, and, notably, adipose-derived stem cells (ADSCs), SVF offers tissue regeneration and repair through the differentiation and secretion of growth factors. Its therapeutic efficacy is due to these cells' synergistic action, prompting extensive research. Methods: This review analyzed the relevant literature on SVF, covering its composition, action mechanisms, clinical applications, and future directions. An extensive literature search from January 2018 to June 2023 was conducted across databases like PubMed, Embase, etc., using specific keywords. Results: The systematic literature search yielded a total of 473 articles. Sixteen articles met the inclusion criteria and were included in the review. This rigorous methodology provides a framework for a thorough and systematic analysis of the existing literature on SVF, offering robust insights into the potential of this important cell population in regenerative medicine. Conclusions: Our review reveals the potential of SVF, a heterogeneous cell mixture, as a powerful tool in regenerative medicine. SVF has demonstrated therapeutic efficacy and safety across disciplines, improving pain, tissue regeneration, graft survival, and wound healing while exhibiting immunomodulatory and anti-inflammatory properties.
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Affiliation(s)
| | | | | | | | - Renat Nurmukhametov
- Neurological Surgery, Peoples Friendship University of Russia, 103274 Moscow, Russia
| | | | - Nicola Montemurro
- Department of Neurosurgery, Azienda Ospedaliero Universitaria Pisana (AOUP), 56100 Pisa, Italy
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14
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Cohen SR, Wesson J. Commentary on: Buccal Fat Pad Augmentation for Midfacial Rejuvenation: Modified Fat Grafting Technique and Ogee Line Remodeling. Aesthet Surg J 2024; 44:131-133. [PMID: 37656019 DOI: 10.1093/asj/sjad284] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2023] [Revised: 08/23/2023] [Accepted: 08/24/2023] [Indexed: 09/02/2023] Open
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15
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Eremin II, Vasiliev VS, Tikhomirov AN, Chibizov PE, Briko AN, Kotenko KV. [Experimental substantiation of medical device design for mechanical processing of adipose tissue]. Khirurgiia (Mosk) 2024:101-108. [PMID: 39665353 DOI: 10.17116/hirurgia2024122101] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2024]
Abstract
OBJECTIVE To substantiate the medical device design for mechanical processing of adipose tissue. MATERIAL AND METHODS Enzymatic method using collagenase and mechanical method for obtaining the stromal vascular fraction (SVF) are compared. The authors emphasized the disadvantages of enzymatic method, such as high cost and duration of process. The main criteria for developing the design were cell viability after processing of adipose tissue and available processing in a minimum number of passages manually without automated mechanical stands. RESULTS The proposed design allows two unidirectional passages to obtain processed lipoaspirate for SVF harvesting. Experimental studies demonstrate that meshes with a minimum cell size of 100 μm allow high cell viability comparable to enzymatic method. Moreover, this design can be used to develop a disposable medical device. CONCLUSION Our results will underlie development of a disposable medical device for mechanical processing of adipose tissue.
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Affiliation(s)
- I I Eremin
- Petrovsky National Research Center of Surgery, Moscow, Russia
| | - V S Vasiliev
- Institute of Plastic Surgery and Cosmetology, Moscow, Russia
| | - A N Tikhomirov
- Bauman Moscow State Technical University, Moscow, Russia
| | - P E Chibizov
- Bauman Moscow State Technical University, Moscow, Russia
| | - A N Briko
- Petrovsky National Research Center of Surgery, Moscow, Russia
| | - K V Kotenko
- Petrovsky National Research Center of Surgery, Moscow, Russia
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16
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Rodriguez-Unda NA, Novak MD, Rohrich RJ. Techniques in Facial Fat Grafting: Optimal Results Based on the Science of Facial Aging. Plast Reconstr Surg 2023; 152:1040e-1043e. [PMID: 36847726 DOI: 10.1097/prs.0000000000010314] [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: 03/01/2023]
Abstract
SUMMARY A thorough understanding of the science of facial aging is imperative to the precise and natural restoration of a youthful appearance. A hallmark of the aging process is fat atrophy. For this reason, fat grafting has become a keystone of the modern face lift. As a result, fat-grafting techniques have been refined to achieve optimal results. This is done through the differential use of fractionated and unfractionated fat throughout the face. This article reviews a single surgeon's technique for achieving optimal results in facial fat grafting.
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Affiliation(s)
- Nelson A Rodriguez-Unda
- From the Division of Plastic Surgery, Department of General Surgery, Baylor Scott-White, Texas A&M College of Medicine
| | - Matthew D Novak
- From the Division of Plastic Surgery, Department of General Surgery, Baylor Scott-White, Texas A&M College of Medicine
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17
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Goncharov EN, Koval OA, Nikolaevich Bezuglov E, Encarnacion Ramirez MDJ, Engelgard M, Igorevich EI, Saporiti A, Valentinovich Kotenko K, Montemurro N. Stromal Vascular Fraction Therapy for Knee Osteoarthritis: A Systematic Review. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:2090. [PMID: 38138193 PMCID: PMC10744886 DOI: 10.3390/medicina59122090] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/01/2023] [Revised: 11/22/2023] [Accepted: 11/26/2023] [Indexed: 12/24/2023]
Abstract
Background and Objectives: Knee osteoarthritis (OA) is a widespread joint disease, set to increase due to aging and rising obesity. Beyond cartilage degeneration, OA involves the entire joint, including the synovial fluid, bones, and surrounding muscles. Existing treatments, such as NSAIDs and corticosteroid injections, mainly alleviate symptoms but can have complications. Joint replacement surgeries are definitive but carry surgical risks and are not suitable for all. Stromal vascular fraction (SVF) therapy is a regenerative approach using cells from a patient's adipose tissue. SVF addresses as degenerative and inflammatory aspects, with potential for cartilage formation and tissue regeneration. Unlike traditional treatments, SVF may reverse OA changes. Being autologous, it reduces immunogenic risks. Materials and Methods: A systematic search was undertaken across PubMed, Medline, and Scopus for relevant studies published from 2017 to 2023. Keywords included "SVF", "Knee Osteoarthritis", and "Regenerative Medicine". Results: This systematic search yielded a total of 172 articles. After the removal of duplicates and an initial title and abstract screening, 94 full-text articles were assessed for eligibility. Of these, 22 studies met the inclusion criteria and were subsequently included in this review. Conclusions: This review of SVF therapy for knee OA suggests its potential therapeutic benefits. Most studies confirmed its safety and efficacy, and showed improved clinical outcomes and minimal adverse events. However, differences in study designs and sizes require a careful interpretation of the results. While evidence supports SVF's positive effects, understanding methodological limitations is key. Incorporating SVF is promising, but the approach should prioritize patient safety and rigorous research.
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Affiliation(s)
| | | | | | | | - Mikhail Engelgard
- Petrovsky Russian Scientific Center of Surgery, 121359 Moscow, Russia
| | | | - Alessandra Saporiti
- Department of Pharmaceuticals, Azienda Usl Toscana Nord Ovest, 56100 Pisa, Italy
| | | | - Nicola Montemurro
- Department of Neurosurgery, Azienda Ospedaliero Universitaria Pisana (AOUP), 56100 Pisa, Italy
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18
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Schipper JAM, van Laarhoven CJHCM, Schepers RH, Tuin AJ, Harmsen MC, Spijkervet FKL, Jansma J, van Dongen JA. Mechanical Fractionation of Adipose Tissue-A Scoping Review of Procedures to Obtain Stromal Vascular Fraction. Bioengineering (Basel) 2023; 10:1175. [PMID: 37892905 PMCID: PMC10604552 DOI: 10.3390/bioengineering10101175] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2023] [Revised: 09/26/2023] [Accepted: 09/28/2023] [Indexed: 10/29/2023] Open
Abstract
Clinical indications for adipose tissue therapy are expanding towards a regenerative-based approach. Adipose-derived stromal vascular fraction consists of extracellular matrix and all nonadipocyte cells such as connective tissue cells including fibroblasts, adipose-derived stromal cells (ASCs) and vascular cells. Tissue stromal vascular fraction (tSVF) is obtained by mechanical fractionation, forcing adipose tissue through a device with one or more small hole(s) or cutting blades between syringes. The aim of this scoping review was to assess the efficacy of mechanical fractionation procedures to obtain tSVF. In addition, we provide an overview of the clinical, that is, therapeutic, efficacy of tSVF isolated by mechanical fraction on skin rejuvenation, wound healing and osteoarthritis. Procedures to obtain tissue stromal vascular fraction using mechanical fractionation and their associated validation data were included for comparison. For clinical outcome comparison, both animal and human studies that reported results after tSVF injection were included. We categorized mechanical fractionation procedures into filtration (n = 4), centrifugation (n = 8), both filtration and centrifugation (n = 3) and other methods (n = 3). In total, 1465 patients and 410 animals were described in the included clinical studies. tSVF seems to have a more positive clinical outcome in diseases with a high proinflammatory character such as osteoarthritis or (disturbed) wound healing, in comparison with skin rejuvenation of aging skin. Isolation of tSVF is obtained by disruption of adipocytes and therefore volume is reduced. Procedures consisting of centrifugation prior to mechanical fractionation seem to be most effective in volume reduction and thus isolation of tSVF. tSVF injection seems to be especially beneficial in clinical applications such as osteoarthritis or wound healing. Clinical application of tSVF appeared to be independent of the preparation procedure, which indicates that current methods are highly versatile.
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Affiliation(s)
- Jan Aart M. Schipper
- Department of Oral & Maxillofacial Surgery, University Medical Center Groningen, University of Groningen, 9713 Groningen, The Netherlands
| | | | - Rutger H. Schepers
- Department of Oral & Maxillofacial Surgery, University Medical Center Groningen, University of Groningen, 9713 Groningen, The Netherlands
| | - A. Jorien Tuin
- Department of Oral & Maxillofacial Surgery, University Medical Center Groningen, University of Groningen, 9713 Groningen, The Netherlands
| | - Marco C. Harmsen
- Department of Pathology & Medical Biology, University Medical Center Groningen, University of Groningen, 9712 Groningen, The Netherlands
| | - Fred K. L. Spijkervet
- Department of Oral & Maxillofacial Surgery, University Medical Center Groningen, University of Groningen, 9713 Groningen, The Netherlands
| | - Johan Jansma
- Department of Oral & Maxillofacial Surgery, University Medical Center Groningen, University of Groningen, 9713 Groningen, The Netherlands
| | - Joris A. van Dongen
- Department of Pathology & Medical Biology, University Medical Center Groningen, University of Groningen, 9712 Groningen, The Netherlands
- Department of Plastic, Reconstructive and Hand Surgery, University Medical Center Utrecht, Utrecht University, 3584 Utrecht, The Netherlands
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19
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Ramaut L, Moonen L, Laeremans T, Aerts JL, Geeroms M, Hamdi M. Push-Through Filtration of Emulsified Adipose Tissue Over a 500-µm Mesh Significantly Reduces the Amount of Stromal Vascular Fraction and Mesenchymal Stem Cells. Aesthet Surg J 2023; 43:NP696-NP703. [PMID: 37130047 DOI: 10.1093/asj/sjad125] [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: 01/24/2023] [Revised: 04/19/2023] [Accepted: 04/20/2023] [Indexed: 05/03/2023] Open
Abstract
BACKGROUND Mechanical isolation of the stromal vascular fraction (SVF) separates the stromal component from the parenchymal cells. Emulsification is currently the most commonly used disaggregation method and is effective in disrupting adipocytes and fragmenting the extracellular matrix (ECM). Subsequent push-through filtration of emulsified adipose tissue removes parts of the ECM that are not sufficiently micronized, thereby further liquifying the tissue. OBJECTIVES The aim of this study was to investigate whether filtration over a 500-µm mesh filter might affect the SVF and adipose-derived mesenchymal stem cell (MSC) quantity in emulsified lipoaspirate samples by removing ECM fragments. METHODS Eleven lipoaspirate samples from healthy nonobese women were harvested and emulsified in 30 passes. One-half of the sample was filtered through a 500-µm mesh filter and the other half was left unfiltered. Paired samples were processed and analyzed by flow cytometry to identify cellular viability, and SVF and MSC yield. RESULTS Push-through filtration reduced the number of SVF cells by a mean [standard deviation] of 39.65% [5.67%] (P < .01). It also significantly reduced MSC counts by 48.28% [6.72%] (P < .01). Filtration did not significantly affect viability (P = .118). CONCLUSIONS Retention of fibrous remnants by push-through filters removed ECM containing the SVF and MSCs from emulsified lipoaspirates. Processing methods should aim either to further micronize the lipoaspirate before filtering or not to filter the samples at all, to preserve both the cellular component carried within the ECM and the inductive properties of the ECM itself.
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20
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Castro-Govea Y, García-Garza JA, Vázquez-Lara SE, González-Cantú CM, Chacón-Moreno H, Cervantes-Kardasch VH. Lipoinjection with Adipose Stem Cells for Nasal Modeling: Rhino Cell, a Highly Versatile Alternative. Arch Plast Surg 2023; 50:335-339. [PMID: 37564724 PMCID: PMC10411243 DOI: 10.1055/a-2067-5481] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2022] [Accepted: 02/15/2023] [Indexed: 04/03/2023] Open
Abstract
It is undeniable that a significant number of patients who want to improve their facial appearance is increasingly interested in nonsurgical procedures. Without a doubt, the use of autologous fat could not be left out as a magnificent alternative for nasal modeling simply because of four influential factors: ease of collection, compatibility, the temporality of the results, and safety. This work describes an innovative alternative technique for nasal modeling using micrografts enriched with adipose-derived mesenchymal stem cells (ASCs). With this technique, fat was collected and divided into two samples, nanofat and microfat. Nanofat was used to isolate the ASCs; microfat was enriched with ASCs and used for nasal modeling. Lipoinjection was performed in a supraperiosteal plane on the nasal dorsum. Through a retrolabial access, the nasal tip and base of the columella were lipoinjected. We consider that nonsurgical nasal modeling using micrografts enriched with ASCs can be an attractive and innovative alternative. This technique will never be a substitute for surgical rhinoplasty. It can be performed in a minor procedure area with rapid recovery and return to the patient's daily activities the next day. If necessary, the procedure can be repeated.
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Affiliation(s)
- Yanko Castro-Govea
- Service of Plastic Surgery, School of Medicine and “Dr. Jose E. González” University Hospital, Autonomous University of Nuevo Leon, Monterrey, Nuevo Leon, Mexico
| | - Jorge A. García-Garza
- Service of Plastic Surgery, School of Medicine and “Dr. Jose E. González” University Hospital, Autonomous University of Nuevo Leon, Monterrey, Nuevo Leon, Mexico
| | - Sergio E. Vázquez-Lara
- Service of Plastic Surgery, School of Medicine and “Dr. Jose E. González” University Hospital, Autonomous University of Nuevo Leon, Monterrey, Nuevo Leon, Mexico
| | - Cynthia M. González-Cantú
- Service of Plastic Surgery, School of Medicine and “Dr. Jose E. González” University Hospital, Autonomous University of Nuevo Leon, Monterrey, Nuevo Leon, Mexico
| | - Hernán Chacón-Moreno
- Service of Plastic Surgery, School of Medicine and “Dr. Jose E. González” University Hospital, Autonomous University of Nuevo Leon, Monterrey, Nuevo Leon, Mexico
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La Padula S, Ponzo M, Lombardi M, Iazzetta V, Errico C, Polverino G, Russo F, D'Andrea L, Hersant B, Meningaud JP, Salzano G, Pensato R. Nanofat in Plastic Reconstructive, Regenerative, and Aesthetic Surgery: A Review of Advancements in Face-Focused Applications. J Clin Med 2023; 12:4351. [PMID: 37445386 DOI: 10.3390/jcm12134351] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2023] [Revised: 06/19/2023] [Accepted: 06/25/2023] [Indexed: 07/15/2023] Open
Abstract
Nanofat is a relatively novel technique in fat grafting that has gained significant interest in the fields of regenerative medicine, aesthetic and translational research. It involves the extraction of autologous fat from a patient, which is then transformed into "nanofat", consisting of small fat particles with a diameter of less than 0.1 mm and containing high concentrations of stem cells and growth factors. This article focuses on the use of nanofat in facial rejuvenation and its potential for lipomodelling. Fat tissue is a "stem cell depot" and nanofat contains many stem cells that can differentiate into various cell types. The Lipogem technology, developed in 2013, enables the isolation of nanofat with an intact perivascular structure, utilizing the high concentration of mesenchymal stromal cells near the pericytes of the adipose vascular system. Nowadays nanofat is used primarily for cosmetic purposes particularly in rejuvenating and improving the appearance of the skin, especially the face. Indeed, it has wide applicability; it can be used to treat fine lines, wrinkles, acne scars, sun-damaged skin, scar repair, and as an alopecia treatment. However, further studies are needed to assess the long-term efficacy and safety of this technique. In conclusion, nanofat is a safe and minimally invasive option for tissue regeneration with considerable therapeutic potential. This study reviews the application and effects of nanofat in regenerative medicine and facial cosmetic surgery.
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Affiliation(s)
- Simone La Padula
- Department of Plastic and Reconstructive Surgery, Federico II University of Naples, Via Pansini 5, 80131 Naples, Italy
- Department of Plastic, Reconstructive and Maxillo-Facial Surgery, Henri Mondor Hospital, University Paris, XII, 51 Avenue du Maréchal de Lattre de Tassigny, 94000 Créteil, France
| | - Martina Ponzo
- Department of Plastic and Reconstructive Surgery, Federico II University of Naples, Via Pansini 5, 80131 Naples, Italy
| | - Mariagiovanna Lombardi
- Department of Plastic and Reconstructive Surgery, Federico II University of Naples, Via Pansini 5, 80131 Naples, Italy
| | - Vincenzo Iazzetta
- Department of Plastic and Reconstructive Surgery, Federico II University of Naples, Via Pansini 5, 80131 Naples, Italy
| | - Concetta Errico
- Department of Plastic and Reconstructive Surgery, Federico II University of Naples, Via Pansini 5, 80131 Naples, Italy
| | - Gianmarco Polverino
- Department of Plastic and Reconstructive Surgery, Federico II University of Naples, Via Pansini 5, 80131 Naples, Italy
| | - Francesca Russo
- Department of Plastic and Reconstructive Surgery, Federico II University of Naples, Via Pansini 5, 80131 Naples, Italy
| | - Luca D'Andrea
- Department of Plastic and Reconstructive Surgery, Federico II University of Naples, Via Pansini 5, 80131 Naples, Italy
| | - Barbara Hersant
- Department of Plastic, Reconstructive and Maxillo-Facial Surgery, Henri Mondor Hospital, University Paris, XII, 51 Avenue du Maréchal de Lattre de Tassigny, 94000 Créteil, France
| | - Jean Paul Meningaud
- Department of Plastic, Reconstructive and Maxillo-Facial Surgery, Henri Mondor Hospital, University Paris, XII, 51 Avenue du Maréchal de Lattre de Tassigny, 94000 Créteil, France
| | - Giovanni Salzano
- Maxillofacial Surgery Unit, Federico II University of Naples, 80131 Naples, Italy
| | - Rosita Pensato
- Department of Plastic and Reconstructive Surgery, Federico II University of Naples, Via Pansini 5, 80131 Naples, Italy
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22
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Yaylacı S, Kaçaroğlu D, Hürkal Ö, Ulaşlı AM. An enzyme-free technique enables the isolation of a large number of adipose-derived stem cells at the bedside. Sci Rep 2023; 13:8005. [PMID: 37198228 DOI: 10.1038/s41598-023-34915-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2022] [Accepted: 05/09/2023] [Indexed: 05/19/2023] Open
Abstract
Adipose tissue derived stromal cells (ADSCs) play a crucial role in research and applications of regenerative medicine because they can be rapidly isolated in high quantities. Nonetheless, their purity, pluripotency, differentiation capacity, and stem cell marker expression might vary greatly depending on technique and tools used for extraction and harvesting. There are two methods described in the literature for isolating regenerative cells from adipose tissue. The first technique is enzymatic digestion, which utilizes many enzymes to remove stem cells from the tissue they reside in. The second method involves separating the concentrated adipose tissue using non-enzymatic, mechanical separation methods. ADSCs are isolated from the stromal-vascular fraction (SVF) of processed lipoaspirate, which is the lipoaspirate's aqueous portion. The purpose of this work was to evaluate a unique device 'microlyzer' for generating SVF from adipose tissue using a mechanical technique that required minimal intervention. The Microlyzer was examined using tissue samples from ten different patients. The cells that were retrieved were characterized in terms of their cell survival, phenotype, proliferation capacity, and differentiation potential. The number of progenitor cells extracted only from the microlyzed tissue was in comparable amount to the number of progenitor cells acquired by the gold standard enzymatic approach. The cells that were collected from each group exhibit similar levels of viability as well as proliferation rates. In addition, the differentiation potentials of the cells derived from the microlyzed tissue were investigated, and it was discovered that cells isolated through microlyzer entered the differentiation pathways more quickly and displayed a greater level of marker gene expression than cells isolated by enzymatic methods. These findings suggest that microlyzer, particularly in regeneration investigations, will allow quick and high rate cell separation at the bedside.
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Affiliation(s)
- Seher Yaylacı
- Department of Medical Biology, Faculty of Medicine, Lokman Hekim University, Ankara, 06800, Turkey.
| | - Demet Kaçaroğlu
- Department of Medical Biology, Faculty of Medicine, Lokman Hekim University, Ankara, 06800, Turkey
| | - Özgür Hürkal
- Plastic Reconstructive and Aesthetic Surgery, Lokman Hekim Hospital, Ankara, 06800, Turkey
| | - Alper Murat Ulaşlı
- Physical Therapy and Rehabilitation, Faculty of Health Sciences, Lokman Hekim University, Ankara, 06800, Turkey
- Romatem Ankara Physical Therapy and Rehabilitation Center, Ankara, 06700, Turkey
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The Composition of Adipose-Derived Regenerative Cells Isolated from Lipoaspirate Using a Point of Care System Does Not Depend on the Subject's Individual Age, Sex, Body Mass Index and Ethnicity. Cells 2022; 12:cells12010030. [PMID: 36611823 PMCID: PMC9818477 DOI: 10.3390/cells12010030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Accepted: 12/20/2022] [Indexed: 12/24/2022] Open
Abstract
Uncultured, unmodified, autologous, adipose-derived regenerative cells (UA-ADRCs) are a safe and effective treatment option for various musculoskeletal pathologies. However, it is unknown whether the composition of the final cell suspension systematically varies with the subject's individual age, sex, body mass index and ethnicity. UA-ADRCs were isolated from lipoaspirate from n = 232 subjects undergoing elective lipoplasty using the Transpose RT system (InGeneron, Inc.; Houston, TX, USA). The UA-ADRCs were assessed for the number of nucleated cells, cell viability and the number of viable nucleated cells per gram of adipose tissue harvested. Cells from n = 37 subjects were further characterized using four-channel flow cytometry. The present study shows, for the first time, that key characteristics of UA-ADRCs can be independent of the subject's age, sex, BMI and ethnicity. This result has important implications for the general applicability of UA-ADRCs in regeneration of musculoskeletal tissue. Future studies must determine whether the independence of key characteristics of UA-ADRCs of the subject's individual age, sex, BMI and ethnicity only applies to the system used in the present study, or also to others of the more than 25 different experimental methods and commercially available systems used to isolate UA-ADRCs from lipoaspirate that have been described in the literature.
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24
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A New Classification for Adipose-derived Stromal-cell Systems. Plast Reconstr Surg Glob Open 2022; 10:e4712. [PMID: 36583163 PMCID: PMC9750561 DOI: 10.1097/gox.0000000000004712] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2022] [Accepted: 10/21/2022] [Indexed: 12/31/2022]
Abstract
Obtaining regenerative cells from adipose tissue and their clinical use has become one of the most popular subjects of plastic surgery. However, there is no accepted classification in terms of methods. In this study, classification is proposed for the first time as a new idea. Accordingly, stromal cells can be obtained from adipose tissue by two approaches: direct methods for the bonds between parenchymal and stromal cells, and indirect methods, which target parenchymal cells rather than strong bonds, and increase the stromal cell ratio relatively. These methods can also be subclassified as fat (+), fat (-), fat (±) in terms of using the remaining fat in the final product as a graft. Direct methods include adinizing and enzymatic techniques; indirect methods include emulsification and micro-fragmentation/micronization techniques. In the enzymatic method, the fat tissue in the final product is considered dirty because it contains enzymes and must be discarded. That is why it is a fat (-) method. The adinizing method using ultra-sharp blades is fat (+) because the adipose tissue after the procedure can be used. Because the fat tissue is exposed to blunt pressure in emulsification techniques, it cannot be used as a graft. Thus, these are fat (-) methods. In micronization techniques using filter systems, there may still be intact adipocytes; therefore, it should be classified as fat (±). Adinizing provides both the highest efficiency and the full use of the end product. This classification will guide clinicians in terms of choosing the right product.
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Vargel İ, Tuncel A, Baysal N, Hartuç-Çevik İ, Korkusuz F. Autologous Adipose-Derived Tissue Stromal Vascular Fraction (AD-tSVF) for Knee Osteoarthritis. Int J Mol Sci 2022; 23:13517. [PMID: 36362308 PMCID: PMC9658499 DOI: 10.3390/ijms232113517] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2022] [Revised: 10/28/2022] [Accepted: 10/30/2022] [Indexed: 07/30/2023] Open
Abstract
Adipose tissue contains adult mesenchymal stem cells that may modulate the metabolism when applied to other tissues. Stromal vascular fraction (SVF) can be isolated from adipose tissue mechanically and/or enzymatically. SVF was recently used to decrease the pain and improve the function of knee osteoarthritis (OA) patients. Primary and/or secondary OA causes inflammation and degeneration in joints, and regenerative approaches that may modify the natural course of the disease are limited. SVF may modulate inflammation and initiate regeneration in joint tissues by initiating a paracrine effect. Chemokines released from SVF may slow down degeneration and stimulate regeneration in joints. In this review, we overviewed articular joint cartilage structures and functions, OA, and macro-, micro-, and nano-fat isolation techniques. Mechanic and enzymatic SVF processing techniques were summarized. Clinical outcomes of adipose tissue derived tissue SVF (AD-tSVF) were evaluated. Medical devices that can mechanically isolate AD-tSVF were listed, and publications referring to such devices were summarized. Recent review manuscripts were also systematically evaluated and included. Transferring adipose tissues and cells has its roots in plastic, reconstructive, and aesthetic surgery. Micro- and nano-fat is also transferred to other organs and tissues to stimulate regeneration as it contains regenerative cells. Minimal manipulation of the adipose tissue is recently preferred to isolate the regenerative cells without disrupting them from their natural environment. The number of patients in the follow-up studies are recently increasing. The duration of follow up is also increasing with favorable outcomes from the short- to mid-term. There are however variations for mean age and the severity of knee OA patients between studies. Positive outcomes are related to the higher number of cells in the AD-tSVF. Repetition of injections and concomitant treatments such as combining the AD-tSVF with platelet rich plasma or hyaluronan are not solidified. Good results were obtained when combined with arthroscopic debridement and micro- or nano-fracture techniques for small-sized cartilage defects. The optimum pressure applied to the tissues and cells during filtration and purification of the AD-tSVF is not specified yet. Quantitative monitoring of articular joint cartilage regeneration by ultrasound, MR, and synovial fluid analysis as well as with second-look arthroscopy could improve our current knowledge on AD-tSVF treatment in knee OA. AD-tSVF isolation techniques and technologies have the potential to improve knee OA treatment. The duration of centrifugation, filtration, washing, and purification should however be standardized. Using gravity-only for isolation and filtration could be a reasonable approach to avoid possible complications of other methodologies.
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Affiliation(s)
- İbrahim Vargel
- Department of Plastic Reconstructive and Aesthetic Surgery, Medical Faculty, Hacettepe University, Altındag, Ankara 06230, Turkey
| | - Ali Tuncel
- Department of Chemical Engineering, Engineering Faculty, Hacettepe University, Universiteler Mahallesi, Hacettepe Beytepe Campus #31, Çankaya, Ankara 06800, Turkey
| | - Nilsu Baysal
- Medical Faculty, Hacettepe University, Altındag, Ankara 06230, Turkey
| | - İrem Hartuç-Çevik
- Department of Sports Medicine, Medical Faculty, Hacettepe University, Altındag, Ankara 06230, Turkey
| | - Feza Korkusuz
- Department of Sports Medicine, Medical Faculty, Hacettepe University, Altındag, Ankara 06230, Turkey
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Liu P, Gurung B, Afzal I, Santin M, Sochart DH, Field RE, Kader DF, Asopa V. The composition of cell-based therapies obtained from point-of-care devices/systems which mechanically dissociate lipoaspirate: a scoping review of the literature. J Exp Orthop 2022; 9:103. [PMID: 36209438 PMCID: PMC9548462 DOI: 10.1186/s40634-022-00537-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Accepted: 09/15/2022] [Indexed: 11/15/2022] Open
Abstract
PURPOSE Cell-based therapies using lipoaspirate are gaining popularity in orthopaedics due to their hypothesised regenerative potential. Several 'point-of-care' lipoaspirate-processing devices/systems have become available to isolate cells for therapeutic use, with published evidence reporting their clinical relevance. However, few studies have analysed the composition of their 'minimally-manipulated' cellular products in parallel, information that is vital to understand the mechanisms by which these therapies may be efficacious. This scoping review aimed to identify devices/systems using mechanical-only processing of lipoaspirate, the constituents of their cell-based therapies and where available, clinical outcomes. METHODS PRISMA extension for scoping reviews guidelines were followed. MEDLINE, Embase and PubMed databases were systematically searched to identify relevant articles until 21st April 2022. Information relating to cellular composition and clinical outcomes for devices/systems was extracted. Further information was also obtained by individually searching the devices/systems in the PubMed database, Google search engine and contacting manufacturers. RESULTS 2895 studies were screened and a total of 15 articles (11 = Level 5 evidence) fulfilled the inclusion criteria. 13 unique devices/systems were identified from included studies. All the studies reported cell concentration (cell number regardless of phenotype per millilitre of lipoaspirate) for their devices/systems (range 0.005-21 × 106). Ten reported cell viability (the measure of live cells- range 60-98%), 11 performed immuno-phenotypic analysis of the cell-subtypes and four investigated clinical outcomes of their cellular products. Only two studies reported all four of these parameters. CONCLUSION When focussing on cell concentration, cell viability and MSC immuno-phenotypic analysis alone, the most effective manual devices/systems were ones using filtration and cutting/mincing. However, it was unclear whether high performance in these categories would translate to improved clinical outcomes. Due to the lack of standardisation and heterogeneity of the data, it was also not possible to draw any reliable conclusions and determine the role of these devices/systems in clinical practice at present. LEVEL OF EVIDENCE Level V Therapeutic.
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Affiliation(s)
- Perry Liu
- South West London Elective Orthopaedic Centre, Epsom, UK.
| | - Binay Gurung
- South West London Elective Orthopaedic Centre, Epsom, UK
| | - Irrum Afzal
- South West London Elective Orthopaedic Centre, Epsom, UK
| | - Matteo Santin
- Centre for Regenerative Medicine and Devices, School of Applied Sciences, University of Brighton, Brighton, UK
| | | | - Richard E Field
- South West London Elective Orthopaedic Centre, Epsom, UK
- University of London, St George's, London, UK
| | - Deiary F Kader
- South West London Elective Orthopaedic Centre, Epsom, UK
| | - Vipin Asopa
- South West London Elective Orthopaedic Centre, Epsom, UK
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27
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Cohen SR, Wesson J, Willens S, Nadeau T, Hillman C, Dobke M, Tiryaki T. Standardized Anatomic and Regenerative Facial Fat Grafting: Objective Photometric Evaluation 1 to 19 Months After Injectable Tissue Replacement and Regeneration. Aesthet Surg J 2022; 42:327-339. [PMID: 34724035 DOI: 10.1093/asj/sjab379] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND A standardized technique for facial fat grafting, injectable tissue replacement and regeneration (ITR2), incorporating new regenerative approaches, was developed to address anatomic volume losses in superficial and deep fat compartments as well as skin aging. OBJECTIVES The aim of this study was to track the short- and long-term effects of facial fat grafting by ITR2 in the midfacial zone over 19 months. METHODS Twenty-nine females were analyzed for midfacial volume changes after autologous fat transfer with ITR2 with varying fat parcel sizes. Volumes were evaluated with an imaging system to calculate differences between a predefined, 3-dimensional midfacial zone measured preoperatively and after fat grafting. RESULTS Patient data were analyzed collectively and by age (<55 and >55 years). Collective analysis revealed a trend of initial volume loss during Months 1 to 7 followed by an increase during Months 8 to 19, averaging 56.6% postoperative gain, and ending at an average of 52.3% gain in volume by 14 to 19 months. A similar trend was observed for patients <55 years of age, with a 54.1% average postoperative gain and a greater final average of 75.2%. Conversely, patients >55 years of age revealed a linear decay from 60.6% to 29.5%. Multiple regression analysis revealed no statistically significant influence of weight change throughout the study. CONCLUSIONS A dynamic change in facial volume was observed, with an initial decrease in facial volume followed by a rebound effect, by 19 months after treatment, of improved facial volume regardless of the amount of fat injected. Volume improvement was greater in patients <55 years old, whereas in patients >55 years old, volume gradually decreased. This study represents the first time that progressive improvement in facial volume has been shown 19 months after treatment. LEVEL OF EVIDENCE: 4
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Affiliation(s)
- Steven R Cohen
- plastic surgeon in private practice in San Diego, CA, USA
| | - Jordan Wesson
- University of California, Los Angeles, Los Angeles, CA, USA
| | - Sierra Willens
- Stanford University School of Medicine, Stanford, CA, USA
| | - Taylor Nadeau
- University of California, San Diego, San Diego, CA, USA
| | | | - Marek Dobke
- Department of Surgery, Division of Plastic Surgery, University of California, San Diego, San Diego, CA, USA
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28
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Copcu HE. Indication-based protocols with different solutions for mechanical stromal-cell transfer. Scars Burn Heal 2022; 8:20595131211047830. [PMID: 35003762 PMCID: PMC8738882 DOI: 10.1177/20595131211047830] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
Background Regenerative medicine is the fastest developing branch of plastic surgery in recent times. Adipose tissue is one of the largest and most important sources in the body for stromal cells. Although mechanical isolation methods are both very popular and have many advantages, they still have no accepted protocols. Objective We developed new protocols called indication-based protocols (IPs) for standardization and new techniques called mechanical stromal-cell transfer (MEST) by using ultra-sharp blades and dilution of adipose tissue with different solutions (saline, Ringer and 5% Dextrose) Methods & material: In order to obtain the desired physical structure (liquid, gel, solid) and the desired volume, four different types of IPs have been defined. Adipose tissue was prediluted with different solutions using 10 or 20 cc injectors in IPs 1 and 2, while condensed adipose tissue was used directly in IPs 3 and 4. Results In MEST, stromal cells were obtained from 100 mL of condensed fat using different IPs with 92% mean viability and cell counts of 26.80–91.90 × 106. Stromal cells can be obtained in the desired form and number of cells by using four different IPs. Conclusion Isolation of stromal cells by cutting fat with sharp blades will prevent the death of fat tissue and stromal cells and will allow high viability and cell count with our new technique. Predilution with different solutions: Diluting the condensed adipose tissue with the desired solutions (saline, Ringer or 5% Dextrose) before the adinizing process will provide even more stromal cells. Lay Summary Obtaining regenerative stromal cells from adipose tissue can be done by two methods: Enzymatic and mechanical. Mechanical methods have many advantages. Although mechanical stromal cell extraction from adipose tissue is very popular and many techniques have been described, there are still no accepted protocols, definition for the end product, and no consensus on the status of the stromal cells. In this study, stromal cells were obtained mechanically by using ultra-sharp blade systems, without exposing adipose tissue to blunt trauma. Thus, a higher number of cells and higher viability could be obtained. An “Indication based” protocol has been defined for the first time in order to obtain the desired number and status (solid, semi-solid, liquid) end product. Diluting the condensed adipose tissue with the desired solutions (saline, Ringer or 5% Dextrose) before the adinizing process will provide even more stromal cells. This will provide an opportunity for clinicians to obtain and apply a stromal cell solution for different indications in different anatomical regions.
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Affiliation(s)
- H Eray Copcu
- Aesthetic, Plastic and Reconstructive Surgery, G-CAT (Gene, Cell and Tissue) Academy, StemRegen Department, Gebze, Kocaeli, Turkey
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30
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Jeyaraman M, Muthu S, Sharma S, Ganta C, Ranjan R, Jha SK. Nanofat: A therapeutic paradigm in regenerative medicine. World J Stem Cells 2021; 13:1733-1746. [PMID: 34909120 PMCID: PMC8641019 DOI: 10.4252/wjsc.v13.i11.1733] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Revised: 05/15/2021] [Accepted: 10/27/2021] [Indexed: 02/06/2023] Open
Abstract
Adipose tissue is a compact and well-organized tissue containing a heterogeneous cellular population of progenitor cells, including mesenchymal stromal cells. Due to its availability and accessibility, adipose tissue is considered a “stem cell depot.” Adipose tissue products possess anti-inflammatory, anti-fibrotic, anti-apoptotic, and immunomodulatory effects. Nanofat, being a compact bundle of stem cells with regenerative and tissue remodeling potential, has potential in translational and regenerative medicine. Considering the wide range of applicability of its reconstructive and regenerative potential, the applications of nanofat can be used in various disciplines. Nanofat behaves on the line of adipose tissue-derived mesenchymal stromal cells. At the site of injury, these stromal cells initiate a site-specific reparative response comprised of remodeling of the extracellular matrix, enhanced and sustained angiogenesis, and immune system modulation. These properties of stromal cells provide a platform for the usage of regenerative medicine principles in curbing various diseases. Details about nanofat, including various preparation methods, characterization, delivery methods, evidence on practical applications, and ethical concerns are included in this review. However, appropriate guidelines and preparation protocols for its optimal use in a wide range of clinical applications have yet to be standardized.
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Affiliation(s)
- Madhan Jeyaraman
- Department of Biotechnology, School of Engineering and Technology, Sharda University , Greater Noida 201306, Uttar Pradesh, India
- Department of Orthopaedics, School of Medical Sciences and Research, Sharda University, Greater Noida 201306, Uttar Pradesh, India
- Indian Stem Cell Study Group, Lucknow 226010, Uttar Pradesh, India
| | - Sathish Muthu
- Department of Biotechnology, School of Engineering and Technology, Sharda University , Greater Noida 201306, Uttar Pradesh, India
- Indian Stem Cell Study Group, Lucknow 226010, Uttar Pradesh, India
- Department of Orthopaedics, Government Medical College and Hospital, Dindigul 624001, Tamil Nadu, India
| | - Shilpa Sharma
- Indian Stem Cell Study Group, Lucknow 226010, Uttar Pradesh, India
- Department of Pediatric Surgery, All India Institute of Medical Sciences, New Delhi 110029, New Delhi, India
| | - Charan Ganta
- Indian Stem Cell Study Group, Lucknow 226010, Uttar Pradesh, India
- Department of Stem Cells and Regenerative Medicine, Kansas State University, Manhattan, United States 10002, United States
| | - Rajni Ranjan
- Department of Orthopaedics, School of Medical Sciences and Research, Sharda University, Greater Noida 201306, Uttar Pradesh, India
| | - Saurabh Kumar Jha
- Department of Biotechnology, School of Engineering and Technology, Sharda University , Greater Noida 201306, Uttar Pradesh, India
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Sharma S, Muthu S, Jeyaraman M, Ranjan R, Jha SK. Translational products of adipose tissue-derived mesenchymal stem cells: Bench to bedside applications. World J Stem Cells 2021; 13:1360-1381. [PMID: 34786149 PMCID: PMC8567449 DOI: 10.4252/wjsc.v13.i10.1360] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Revised: 07/02/2021] [Accepted: 08/30/2021] [Indexed: 02/06/2023] Open
Abstract
With developments in the field of tissue engineering and regenerative medicine, the use of biological products for the treatment of various disorders has come into the limelight among researchers and clinicians. Among all the available biological tissues, research and exploration of adipose tissue have become more robust. Adipose tissue engineering aims to develop by-products and their substitutes for their regenerative and immunomodulatory potential. The use of biodegradable scaffolds along with adipose tissue products has a major role in cellular growth, proliferation, and differentiation. Adipose tissue, apart from being the powerhouse of energy storage, also functions as the largest endocrine organ, with the release of various adipokines. The progenitor cells among the heterogeneous population in the adipose tissue are of paramount importance as they determine the capacity of regeneration of these tissues. The results of adipose-derived stem-cell assisted fat grafting to provide numerous growth factors and adipokines that improve vasculogenesis, fat graft integration, and survival within the recipient tissue and promote the regeneration of tissue are promising. Adipose tissue gives rise to various by-products upon processing. This article highlights the significance and the usage of various adipose tissue by-products, their individual characteristics, and their clinical applications.
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Affiliation(s)
- Shilpa Sharma
- Department of Pediatric Surgery, All India Institute of Medical Sciences, New Delhi 110029, India
- Indian Stem Cell Study Group, Lucknow, Uttar Pradesh 226010, India
| | - Sathish Muthu
- Indian Stem Cell Study Group, Lucknow, Uttar Pradesh 226010, India
- Department of Orthopaedics, Government Medical College and Hospital, Dindigul, Tamil Nadu 624304, India
- Research Scholar, Department of Biotechnology, School of Engineering and Technology, Greater Noida, Sharda University, Uttar Pradesh 201306, India
| | - Madhan Jeyaraman
- Indian Stem Cell Study Group, Lucknow, Uttar Pradesh 226010, India
- Research Scholar, Department of Biotechnology, School of Engineering and Technology, Greater Noida, Sharda University, Uttar Pradesh 201306, India
- Department of Orthopaedics, School of Medical Sciences and Research, Sharda University, Greater Noida, Uttar Pradesh 201306, India
| | - Rajni Ranjan
- Department of Orthopaedics, School of Medical Sciences and Research, Sharda University, Greater Noida, Uttar Pradesh 201306, India
| | - Saurabh Kumar Jha
- Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida, Uttar Pradesh 201306, India
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Ng KLB, Hsieh MCW, Lin YN, Chen RF, Lin TM, Lin SD, Kuo YR. Application of nanofat grafting to rescue a severe ischaemic hand with thromboangiitis obliterans: A case report about promising salvage procedure. Medicine (Baltimore) 2021; 100:e27577. [PMID: 34678903 PMCID: PMC8542167 DOI: 10.1097/md.0000000000027577] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Accepted: 10/07/2021] [Indexed: 11/25/2022] Open
Abstract
RATIONALE Currently, there is no consensus regarding the best treatment for patients with thromboangiitis obliterans (TAO). Regenerative medicine, such as bone marrow stem cells or adipose-derived stem cell (ASC) transplantation, have proven efficacy in improving tissue perfusion and wound healing in clinical trials. In this case, we used nanofat grafting to treat severe conditions in a patient with TAO, with promising outcomes. PATIENT CONCERNS This is a case of a 48-year-old smoker who presented with cyanosis in both hands and the right foot, with gangrenous changes. Investigative angiography showed severe vasospasm in the radial and ulnar arteries of the patient's left hand. Progressive cyanosis of the patient's left hand was noted which may eventually require amputation if left untreated. DIAGNOSES He was diagnosed with TAO under the Shionoya diagnostic criteria. INTERVENTIONS Fasciotomy and necrotic tissue debridement were performed, followed by centrifuged nanofat grafting. The nanofat graft was prepared using Pallua method and deployed with a MAFT-GUN (Dermato Plastica Beauty Co., Ltd., Kaohsiung, Taiwan). OUTCOMES Three months later, computed tomography angiography revealed a radial artery patency. The patient's wrist function was preserved with uneventful wound healing. LESSONS The regenerative ability of centrifuged nanofat grafts not only helps wound healing but also helps reverse vasospasm and preserve remnant tissue perfusion.
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Affiliation(s)
- Kwan Lok Benjamin Ng
- Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung City, Taiwan
| | - Meng-Chien Willie Hsieh
- Division of Plastic Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung City, Taiwan
| | - Yun-Nan Lin
- Division of Plastic Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung City, Taiwan
| | - Rong-Fu Chen
- Division of Plastic Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung City, Taiwan
| | - Tsai-Ming Lin
- Division of Plastic Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung City, Taiwan
- Charming Institute of Aesthetic and Regenerative Surgery (CIARS), Kaohsiung City, Taiwan
| | - Sin-Daw Lin
- Division of Plastic Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung City, Taiwan
- Department of Surgery, Kaohsiung Municipal Siaogang Hospital, Kaohsiung City, Taiwan
| | - Yur-Ren Kuo
- Division of Plastic Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung City, Taiwan
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Three states of stromal cells-solid, liquid, and aerosol-and innovative delivery methods not previously reported. Arch Plast Surg 2021; 48:549-552. [PMID: 34583444 PMCID: PMC8490114 DOI: 10.5999/aps.2021.00311] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Accepted: 05/17/2021] [Indexed: 12/27/2022] Open
Abstract
Clinical applications of stromal cells obtained mechanically from adipose tissue are quite popular methods. However, generally accepted protocols still do not exist. In this study, three new delivery methods using different protocols are presented as innovative methods in accordance with an approach called “Indication-based protocols.” In mechanical methods, before cutting the fat tissue with ultra-sharp blades, which we define as “Adinizing,” mixing it with different liquids such as saline or plasma provides the stromal cells in liquid form with high number and viability as a final product. At the same time, since stromal cells and extracellular matrix are preserved by mechanical methods, it was deemed appropriate to use the term total stromal cells (TOST) instead of stromal vascular fraction for this final product, unlike the product obtained with the enzyme. TOST can be combined with plasma and used for dermal filling in “solid” form. In addition to this filling effect, it will also cause a change in the tissue regeneratively. Finally, the stromal cells obtained from liquid can be applied clinically in aerosol form with the help of nebulizer. We believe that three innovative delivery methods can be used successfully in the treatment of many clinical situations in the future.
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Crowley JS, Kream E, Fabi S, Cohen SR. Facial Rejuvenation With Fat Grafting and Fillers. Aesthet Surg J 2021; 41:S31-S38. [PMID: 34002771 DOI: 10.1093/asj/sjab014] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Facial rejuvenation requires a multi-modality approach to address the sun damage, volume loss, and thinning of skin that occurs with aging. With age, the collagen fibrils that provide strength become fragmented and fibroblasts connections become weak, leading to skin laxity and loss of youthful skin. Fillers can lead to a more youthful appearance by providing volumetric support. Synthetic fillers such as hyaluronic acid products, calcium hydroxyapatite, polylactic acid, and polymethylmethacralate have bio-stimulatory affects, ranging from small effects on fibroblast production to prolonged stimulatory effects on dermal thickness and blood supply. Fat grafting is also an ideal technique for facial rejuvenation because it is readily available, natural, and has regenerative effects. This review describes a new technique of fat grafting for the face called Injectable Tissue Replacement and Regeneration that specifically addresses the different anatomic compartments of the face with volume loss. With this brief review, we aim to evaluate the currents trends of fat grafting and fillers in the management of facial rejuvenation, including the cellular changes that occur with facial aging, the bio-stimulatory effects of fillers, and the anatomic replacement of tissue with fat grafting. >Level of Evidence: 4.
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Affiliation(s)
- J Sarah Crowley
- Division of Plastic Surgery, University of California San Diego, San Diego, CA, USA
| | - Elizabeth Kream
- Department of Dermatology, University of Illinois College of Medicine, Chicago, IL, USA
| | - Sabrina Fabi
- Division of Dermatology, University of California San Diego, La Jolla, CA, USA
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Cohen SR, Hewett S, Baraf P, Crowley SJ, Atlan M. Facelift With Power-Assisted Dissection: A Preliminary Report. Aesthet Surg J 2021; 41:641-651. [PMID: 32722753 DOI: 10.1093/asj/sjaa213] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Subcutaneous elevation of the skin has remained a key component in all facelift techniques. OBJECTIVES The aim of this preliminary report was to introduce the ABC facelift as a 3-step method addressing photodamage, soft tissue laxity, and areas of bone and volume loss. METHODS The procedure consists of: (A) anatomic and regenerative adipose grafting prior to skin elevation; (B) the use of a Baraf elevator for takedown of perpendicular subcutaneous fibers following hydrodissection of the skin flaps with tumescent solution; and (C) cautery dissection of the superficial muscular aponeurotic system (SMAS) and platysma in the neck. RESULTS Thirty-four patients (31 females; 3 male), aged 50 to 77 years at the date of procedure, underwent an ABC facelift. Dissection of the skin flaps and SMAS elevation were faster than with traditional methods, averaging 10 to 15 minutes per hemiface. Bleeding was reduced (average estimated blood loss, 12 mL) and the skin flaps appeared better perfused with less venous engorgement and ecchymosis than achieved with sharp scissor dissection. In general, patients appeared to have shorter postoperative recovery courses and less social downtime secondary to bruising and edema. CONCLUSIONS The ABC facelift addresses facial laxity, volume loss, and skin aging with 3 simple steps: anatomic and regenerative fat grafting, combined with power-assisted dissection of the skin and cautery elevation of the SMAS. The use of more advanced hydrodissection tools to achieve further improvements in layer separation is currently being investigated. LEVEL OF EVIDENCE: 4
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Affiliation(s)
| | - Sierra Hewett
- Stanford University, School of Medicine, Stanford, CA, USA
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Copcu HE, Oztan S. Not Stromal Vascular Fraction (SVF) or Nanofat, but Total Stromal-Cells (TOST): A New Definition. Systemic Review of Mechanical Stromal-Cell Extraction Techniques. Tissue Eng Regen Med 2021; 18:25-36. [PMID: 33231864 PMCID: PMC7862455 DOI: 10.1007/s13770-020-00313-0] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2020] [Revised: 10/04/2020] [Accepted: 10/19/2020] [Indexed: 12/25/2022] Open
Abstract
The most important and greatest source in the body for regenerative cells is fat tissue. Obtaining regenerative cells from adipose tissue can be done in two ways: Enzymatic and mechanical. The regenerative cell cocktail obtained by the enzymatic method, including stem cells, is called Stromal vascular fracture (SVF). In the literature, there is no clear definition of regenerative cells obtained by mechanical method. We systematically searched the techniques and definitions for stromal cells obtained from adipose tissue by scanning different databases. To evaluate the mechanical stromal-cell isolation techniques and end products from adipose tissue. Systematic review of English and non-English articles using Embase, PubMed, Web of Science and Google scholar databases. Search terms included Nanofat, fragmented fat, mechanical stromal / stem cell, mechanical SVF, SVF gel. We screened all peer-reviewed articles related with mechanical stromal-cell isolation. Author performed a literature query with the aforementioned key words and databases. A total of 276 publications containing the keywords we searched were reached. In these publications, there are 46 different definitions used to obtain mechanical stromal cells. The term SVF is only suitable for enzymatic methods. A different definition is required for mechanical. The most used term nanofat is also not suitable because the product is not in both "fat" and in "nanoscale". We think that the term total stromal-cells would be the most appropriate definition since both extracellular matrix and all stromal cells are protected in mechanical methods.
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Affiliation(s)
- H. Eray Copcu
- Plastic and Reconstructive Surgery, MEST Medical Services, Cumhuriyet Bulv. No:161/A,1,2 Alsancak, Izmir, Turkey
| | - Sule Oztan
- Plastic and Reconstructive Surgery, MEST Medical Services, Cumhuriyet Bulv. No:161/A,1,2 Alsancak, Izmir, Turkey
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Cohen SR, Hewett S. Commentary on: Fat Grafting to Improve Results of Facelift: Systematic Review of Safety and Effectiveness of Current Treatment Paradigms. Aesthet Surg J 2021; 41:13-15. [PMID: 32556099 DOI: 10.1093/asj/sjaa043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Affiliation(s)
- Steven R Cohen
- Dr Cohen is a Clinical Professor of Plastic Surgery, University of California, San Diego, CA
| | - Sierra Hewett
- Ms Hewett is a research assistant at a private plastic surgery practice in La Jolla, CA
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Copcu HE, Oztan S. New Mechanical Fat Separation Technique: Adjustable Regenerative Adipose-tissue Transfer (ARAT) and Mechanical Stromal Cell Transfer (MEST). Aesthet Surg J Open Forum 2020; 2:ojaa035. [PMID: 33791661 PMCID: PMC7780457 DOI: 10.1093/asjof/ojaa035] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/16/2020] [Indexed: 02/06/2023] Open
Abstract
Background Adipose tissue is not only a very important source of filler but also the body's greatest source of regenerative cells. Objectives In this study, adipose tissue was cut to the desired dimensions using ultra-sharp blade systems to avoid excessive blunt pressure and applied to various anatomical areas-a procedure known as adjustable regenerative adipose-tissue transfer (ARAT). Mechanical stromal cell transfer (MEST) of regenerative cells from fat tissue was also examined. Methods ARAT, MEST, or a combination of these was applied in the facial area of a total of 24 patients who were followed for at least 24 months. The integrity of the fat tissue cut with different diameter blades is shown histopathologically. The number and viability of the stromal cells obtained were evaluated and secretome analyses were performed. Patient and surgeon satisfaction were assessed with a visual analog scale. Results With the ARAT technique, the desired size fat grafts were obtained between 4000- and 200-micron diameters and applied at varying depths to different aesthetic units of the face, and a guide was developed. In MEST, stromal cells were obtained from 100 mL of condensed fat using different indication-based protocols with 93% mean viability and cell counts of 28.66 to 88.88 × 106. Conclusions There are 2 main complications in fat grafting: visibility in thin skin and a low retention rate. The ARAT technique can be used to prevent these 2 complications. MEST, on the other hand, obtains a high rate of fat and viable stromal cells without applying excessive blunt pressure. Level of Evidence 4
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Affiliation(s)
- H Eray Copcu
- Department of Plastic and Reconstructive Surgery, MEST Medical Services, Izmir, Turkey
| | - Sule Oztan
- Department of Plastic and Reconstructive Surgery, MEST Medical Services, Izmir, Turkey
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Alt EU, Winnier G, Haenel A, Rothoerl R, Solakoglu O, Alt C, Schmitz C. Towards a Comprehensive Understanding of UA-ADRCs (Uncultured, Autologous, Fresh, Unmodified, Adipose Derived Regenerative Cells, Isolated at Point of Care) in Regenerative Medicine. Cells 2020; 9:E1097. [PMID: 32365488 PMCID: PMC7290808 DOI: 10.3390/cells9051097] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2020] [Revised: 04/18/2020] [Accepted: 04/21/2020] [Indexed: 02/06/2023] Open
Abstract
It has become practically impossible to survey the literature on cells derived from adipose tissue for regenerative medicine. The aim of this paper is to provide a comprehensive and translational understanding of the potential of UA-ADRCs (uncultured, unmodified, fresh, autologous adipose derived regenerative cells isolated at the point of care) and its application in regenerative medicine. We provide profound basic and clinical evidence demonstrating that tissue regeneration with UA-ADRCs is safe and effective. ADRCs are neither 'fat stem cells' nor could they exclusively be isolated from adipose tissue. ADRCs contain the same adult stem cells ubiquitously present in the walls of blood vessels that are able to differentiate into cells of all three germ layers. Of note, the specific isolation procedure used has a significant impact on the number and viability of cells and hence on safety and efficacy of UA-ADRCs. Furthermore, there is no need to specifically isolate and separate stem cells from the initial mixture of progenitor and stem cells found in ADRCs. Most importantly, UA-ADRCs have the physiological capacity to adequately regenerate tissue without need for more than minimally manipulating, stimulating and/or (genetically) reprogramming the cells for a broad range of clinical applications. Tissue regeneration with UA-ADRCs fulfills the criteria of homologous use as defined by the regulatory authorities.
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Affiliation(s)
- Eckhard U. Alt
- Heart and Vascular Institute, Department of Medicine, Tulane University Health Science Center, New Orleans, LA 70112, USA
- Sanford Health, University of South Dakota, Sioux Falls, SD 57104, USA
- University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA
- Isar Klinikum Munich, 80331 Munich, Germany
- InGeneron, Inc., Houston, TX 77054, USA
| | | | - Alexander Haenel
- Heart and Vascular Institute, Department of Medicine, Tulane University Health Science Center, New Orleans, LA 70112, USA
- Department of Radiology and Nuclear Medicine, University Hospital Schleswig-Holstein, 23562 Lübeck, Germany
| | | | - Oender Solakoglu
- Dental Department of the University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
- Periodontology and Implant Dentistry, 22453 Hamburg, Germany
| | | | - Christoph Schmitz
- Institute of Anatomy, Faculty of Medicine, LMU Munich, 80331 Munich, Germany
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