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Efficacy of stromal vascular fraction for knee osteoarthritis:A prospective,single-centre,non-randomized study with 2 years follow-up

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World Journal of Orthopedics 2024年第5期15卷 457-468页

作者： Madhan Jeyaraman Naveen Jeyaraman Tarun Jayakumar Swaminathan Ramasubramanian Rajni Ranjan Saurabh Kumar Jha Ashim Gupta Department of Orthopaedics ACS Medical College and HospitalDr MGR Educational and Research InstituteChennaiTamil Nadu 600077India Department of Biotechnology School of Engineering and TechnologySharda UniversityGreater NoidaUttar Pradesh 201310India Department of Orthopaedics and Regenerative Medicine South Texas Orthopaedic Research InstituteLaredoTX 78045United States Department of Orthopaedics KIMS-Sunshine HospitalHyderabadTelangana 500032India Department of Orthopaedics Government Medical CollegeOmandurar Government EstateChennaiTamil Nadu 600002India Department of Orthopaedics School of Medical Sciences and ResearchSharda UniversityGreater NoidaUttar Pradesh 201306India Department of Zoology Kalindi CollegeUniversity of DelhiNew Delhi 110008India Department of Orthopaedics and Regenerative Medicine Regenerative OrthopaedicsNoida 201301Uttar PradeshIndia Department of Orthopaedics and Regenerative Medicine Future BiologicsLawrencevilleGA 30043United States Department of Orthopaedics and Regenerative Medicine BioIntegrateLawrencevilleGA 30043United States

BACKGROUND Current osteoarthritis(OA)treatments focus on symptom relief without addressing the underlying disease process.In regenerative medicine,current treatments have limitations.In regenerative medicine,more research is needed for intra-articular stromal vascular fraction(SVF)injections in OA,including dosage optimization,long-term efficacy,safety,comparisons with other treatments,and mechanism exploration.AIM To compare the efficacy of intra-articular SVF with corticosteroid(ICS)injections in patients with primary knee OA.METHODS The study included 50 patients with Kellgren-Lawrence grades II and III OA.Patients were randomly assigned(1:1)to receive either a single intra-articular SVF injection(group A)or a single intra-articular ICS(triamcinolone)(group B)injection.Patients were followed up at 1,3,6,12,and 24 months.Visual analog score(VAS)and International Knee Documentation Committee(IKDC)scores were administered before the procedure and at all followups.The safety of SVF in terms of adverse and severe adverse events was recorded.Statistical analysis was performed with SPSS Version 26.0,IBM Corp,Chicago,IL,United States.RESULTS Both groups had similar demographics and baseline clinical characteristics.Follow-up showed minor patient loss,resulting in 23 and 24 in groups A and B respectively.Group A experienced a notable reduction in pain,with VAS scores decreasing from 7.7 to 2.4 over 24 months,compared to a minor reduction from 7.8 to 6.2 in Group B.This difference in pain reduction in group A was statistically significant from the third month onwards.Additionally,Group A showed significant improvements in knee functionality,with IKDC scores rising from 33.4 to 83.10,whereas Group B saw a modest increase from 36.7 to 45.16.The improvement in Group A was statistically significant from 6 months and maintained through 24 months.CONCLUSION Our study demonstrated that intra-articular administration of SVF can lead to reduced pain and improved knee function in patients with primary knee OA.More adequately powe

关键词： Knee osteoarthritis Adipose tissue stromal vascular fraction Regenerative medicine Orthobiologics

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Non-enzymatic methods for isolation of stromal vascular fraction and adipose-derived stem cells:A systematic review

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World Journal of Methodology 2024年第2期14卷 134-144页

作者： Vamsi Krishna Mundluru MJ Naidu Ravi Teja Mundluru Naveen Jeyaraman Sathish Muthu Swaminathan Ramasubramanian Madhan Jeyaraman Department of Orthopaedics MJ Naidu Super Speciality HospitalVijayawada 520002Andhra PradeshIndia Department of Regenerative Medicine StemC ClinicsVijayawada 520002Andhra PradeshIndia Department of Orthopaedics ACS Medical College and HospitalDr.MGR Educational and Research InstituteChennai 600077Tamil NaduIndia Department of Orthopaedics Orthopaedic Research GroupCoimbatore 641045Tamil NaduIndia Department of Orthopaedics Government Medical College and HospitalKarur 639004Tamil NaduIndia Department of Biotechnology Faculty of EngineeringKarpagam Academy of Higher EducationCoimbatore 641021Tamil NaduIndia Department of Orthopaedics Government Medical CollegeOmandurar Government EstateChennai 600002Tamil NaduIndia

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 regulatory complexities.AIM This systematic review aimed to assess the efficacy and practicality of nonenzymatic,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 medic

关键词： Adipose-derived stem cells stromal vascular fraction Regenerative medicine Non-enzymatic isolation Mechanical separation techniques

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Intra-articular injection of stromal vascular fraction for knee degenerative joint disease:a concise review of preclinical and clinical evidence

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Science China(Life Sciences) 2022年第10期65卷 1959-1970页

作者： Yuan Liu Liping Huang Yi Zeng Mingyang Li Huiqi Xie Bin Shen Orthopedics Research Institute Department of OrthopedicsNational Clinical Research Center for GeriatricsWest China HospitalSichuan UniversityChengdu 610041China Laboratory of Stem Cell and Tissue Engineering Orthopedic Research InstituteMed-X Center for MaterialsState Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China

Autologous fat-derived stromal vascular fraction(SVF) is a mixed cell population that has been used for many years in regenerative plastic surgery.In terms of animal and clinical research,this concise review was performed to evaluate the efficacy of SVF in knee degenerative joint disease(KDJD),which could cause pain,disability and severely affect patients’ lives.Thirteen studies retrieved and screened from the databases were included,including six animal studies and seven clinical trials.The metaanalysis of clinical research shows that intra-articular injection of SVF,in combination with adjuvant surgery,could alleviate pain and improve early functional recovery for patients with KDJD at Kellgren-Lawrence(KL) grades Ⅱ–Ⅲ.

关键词： stromal vascular fraction knee degenerative joint disease meta-analysis review

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Combination of stromal vascular fraction and Ad-COMP-Angl gene therapy improves long-term therapeutic efficacy for diabetes-induced erectile dysfunction

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Asian Journal of Andrology 2018年第5期20卷 465-472页

作者： Guo-Nan Yin Lin Wang Xiang Nan Lin Lei Shi Zhen-Lin Gao Feng-Chan Han Ping Li Yin-Chuan Jin Jun-Kyu Suh Ji-Kan Ryu Xiong Wang Hai Rong Jin National Research Center for Sexual Medicine and Department of Urology Inha University School of Medicine Incheon 22332 Korea Department of Urology Yantai Yuhuangding Hospital Affiliated to Medical College of Qingdao University Yantai 264000 China Key Laboratory for Genetic Hearing Disorders in Shandong Binzhou Medical University Yantai 264003 China Department of Histology and Embryology Binzhou Medical University Yantai Shandong 264000 China Reproductive Medicine Center Affiliated Yantai Yuhuangding Hospital of Qingdao University Yantai 264000 China

Men with diabetic erectile dysfunction （ED） respond poorly to the currently available oral phosphodiesterase-5 inhibitors. Therefore, functional therapies for diabetic ED are needed. stromal vascular fraction （SVF） and the adenovirus-mediated cartilage oligomeric matrix angiopoietin-1 （Ad-COMP-Angl） gene are known to play critical roles in penile erection. We previously reported that SVF and Ad-COMP-Ang1 have only a short-term effect in restoring erectile function. Further improvements to ED therapy are needed for long-lasting effects. In the present study, we aimed to test if the combination of SVF and Ad-COMP-Ang1 could extend the erection effect in diabetic ED. We found that the combination therapy showed a long-term effect in restoring erectile function through enhanced penile endothelial and neural cell regeneration. Combination therapy with SVF and Ad-COMP-Angl notably restored cavernous endothelial cell numbers, pericyte numbers, endothelial cell-cell junctions, decreased cavernous endothelial cell permeability, and promoted neural regeneration for at least 4 weeks in diabetic mice, In summary, this is an initial description of the long-term effect of combination therapy with SVF and Ad-COMP-Ang1 in restoring erectile function through a dual effect on endothelial and neural cell regeneration. Such combination therapy may have therapeutic potential for the treatment of diabetic ED.

关键词： angiopoietin-1 erectile dysfunction neural cell regeneration stromal vascular fraction

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Activity of the Mechanically Isolated Hybrid stromal vascular fraction on Osteoarthritis

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International Journal of Clinical Medicine 2023年第11期14卷 505-524页

作者： Polen Koçak Serli Canikyan Yağiz Denizci Burak Beksaç Yaren Kul Tunç Tiryaki Biomedical Engineering Istinye University Istanbul Turkey Genetics and Bioengineering Yeditepe University Istanbul Turkey Faculty of Medicine Medipol University Istanbul Turkey Private Practise Clinic Istanbul Turkey Bioengineering Yildiz Technical University Istanbul Turkey Cadogan Clinic London UK

Background: Regenerative medicine holds promise for treating degenerative and inflammatory conditions like osteoarthritis (OA). However, the complex molecular mechanisms of OA and the limitations of current therapies remain challenges. Adipose-derived stem cells (ADSC) and stromal vascular fraction (SVF) are gaining attention for OA treatment due to their abundance in adipose tissue. The literature delineates two primary techniques for SVF extraction from adipose tissue: enzymatic digestion and mechanical methods. The Lipocube Hybrid SVF presents a straightforward and secure mechanical isolation method for SVF, enhancing its regenerative potential for various applications. Purpose: This study aims to provide valuable insights into the potential of Lipocube Hybrid SVF as a regenerative therapy for OA, contributing to the broader understanding of its applicability in addressing this debilitating condition. Method: To assess the effectiveness and safety of the Lipocube Hybrid SVF, we have designed a comparative study that evaluates cellular activity and viability, phenotypic characterization, and differentiation potential. The in vitro activity of mechanically isolated SVF is compared to the established gold standard enzymatic digestion method. After in vitro studies, Lipocube Hybrid mechanical isolation method was used to isolate SVF and applied in 42 knee and 7 hip joints of 28 patients with Grade II, Grade III, and Grade IV OA. Results: The Lipocube Hybrid group had slightly lower viable cell numbers but higher cell viability. Flow cytometry analysis showed the Lipocube Hybrid group exhibited more favorable markers for regenerative potential and reduced inflammatory response. Additionally, both groups demonstrated successful osteogenic differentiation, with the Lipocube Hybrid group excelling in chondrogenic and adipogenic differentiation. The clinical application of the Lipocube Hybrid SVF in OA patients resulted in significant improvements in WOMAC and VAS scores across different OA grades. Conclusions: This co

关键词： Osteoarthritis stromal vascular fraction Enzymatic Isolation Mechanical Isolation Regenerative Medicine

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Adipose-derived regenerative therapies for the treatment of knee osteoarthritis

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World Journal of Stem Cells 2024年第4期16卷 324-333页

作者： Ilias E Epanomeritakis Wasim S Khan Division of Trauma and Orthopaedic Surgery Addenbrooke’s HospitalCambridge University Hospitals NHS Foundation TrustCambridge CB20QQUnited Kingdom Division of Trauma and Orthopaedic Surgery Department of SurgeryUniversity of CambridgeCambridge CB20QQUnited Kingdom

Knee osteoarthritis is a degenerative condition with a significant disease burden and no disease-modifying therapy.Definitive treatment ultimately requires joint replacement.Therapies capable of regenerating cartilage could significantly reduce financial and clinical costs.The regenerative potential of mesenchymal stromal cells(MSCs)has been extensively studied in the context of knee osteoarthritis.This has yielded promising results in human studies,and is likely a product of immunomodulatory and chondroprotective biomolecules produced by MSCs in response to inflammation.Adipose-derived MSCs(ASCs)are becoming increasingly popular owing to their relative ease of isolation and high proliferative capacity.stromal vascular fraction(SVF)and micro-fragmented adipose tissue(MFAT)are produced by the enzymatic and mechanical disruption of adipose tissue,respectively.This avoids expansion of isolated ASCs ex vivo and their composition of heterogeneous cell populations,including immune cells,may potentiate the reparative function of ASCs.In this editorial,we comment on a multicenter randomized trial regarding the efficacy of MFAT in treating knee osteoarthritis.We discuss the study’s findings in the context of emerging evidence regarding adipose-derived regenerative therapies.An underlying mechanism of action of ASCs is proposed while drawing important distinctions between the properties of isolated ASCs,SVF,and MFAT.

关键词： Knee osteoarthritis Mesenchymal stromal cells Adipose tissue stromal vascular fraction Micro-fragmented adipose tissue Regeneration

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Evaluation of TransFix^(■) Mediated Stabilisation of Adipose-Derived stromal vascular fraction for Delayed Flow Cytometry Analysis

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Open Journal of Regenerative Medicine 2014年第3期3卷 54-63页

作者： Elisabeth Karsten Judy Sung Charlotte Morgan Benjamin Herbert Graham Vesey Regeneus Ltd. SydneyAustralia

The increasing implementation of multicentre studies has led to a need for the optimization of a method that allows for accurate post-hoc analysis of patient biological samples. Assessment of total cell number, viability and immunophenotype can present logistical challenges which can be aided by batch processing. The increased sample storage time that this requires necessitates the use of reagents to preserve cellular integrity, viability and immunophenotype. TransFix is a stabilising reagent that has been developed for the preservation of cell numbers and cell marker expression in peripheral whole blood for up to ten days. This study investigated the use of TransFix reagent for the preservation of the stromal vascular fraction (SVF) of collagenase digested adipose tissue. It was demonstrated that TransFix was suitable for accurately measuring nucleated SVF cell numbers for up to seven days as well as back calculating original cell viability. It also stabilised three CD markers commonly used to identify populations within SVF (CD90, CD31 and CD45) for up to seven days. There was no significant difference between the number of CD90, CD31 and CD45 positive cells after stabilisation at Day 7 compared to Day 0 unstabilised samples. The results suggest that TransFix can be used to preserve a biological mixed cell population from human adipose-derived SVF for up to seven days for accurate post-hoc analysis.

关键词： TransFix^(■) Adipose Tissue stromal vascular fraction Immunophenotyping

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Fat Grafting for Rejuvenation and Regeneration with stromal vascular fraction Gel

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Chinese Journal Of Plastic and Reconstructive Surgery 2020年第3期2卷 181-186页

作者： Wenqing JIANG Yunjun LIAO Feng LU Department of Plastic and Cosmetic Surgery Nanfang HospitalSouthern Medical UniversityGuangzhou 510515China.

Lipotransfer has become a powerful regenerative tool,largely because of its cellular components,the stromal vascular fraction(SVF).However,the clinical separation of cells with collagenase is strictly legislated.In 2017,Yao et al.postulated a novel fat-derived product mechanically concentrating SVF cells and an extracellular matrix(ECM)and named it stromal vascular fraction gel(SVF-gel).This review discussed the protocol of SVF-gel and its component as well as its inner structure.The histologic examination and the retention rate after the transplantation of SVF-gel were also rendered.Moreover,we summed up the rejuvenating and regenerative use of SVF-gel and introduced its possible mechanism.

关键词： Fat grafting stromal vascular fraction Rejuvenation Regeneration Cell-based therapy

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Therapeutic applications of adipose-derived stromal vascular fractions in osteoarthritis

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World Journal of Stem Cells 2022年第10期14卷 744-755页

作者： Qi Tang Xian-Sheng Zhao Ao Guo Ruo-Tong Cui Huai-Le Song Zi-Yang Qi Yi Pan Yue Yang Fang-FangZhang Liang Jin School of Life Science and Technology China Pharmaceutical UniversityNanjing 211198Jiangsu ProvinceChina Department of Dermatology Huashan HospitalFudan UniversityShanghai 200040China

Osteoarthritis(OA)is considered to be a highly heterogeneous disease with progressive cartilage loss,subchondral bone remodeling,and low-grade inflammation.It is one of the world's leading causes of disability.Most conventional clinical treatments for OA are palliative drugs,which cannot fundamentally cure this disease.The stromal vascular fraction(SVF)from adipose tissues is a heterogeneous cell population.According to previous studies,it contains a large number of mesenchymal stem cells,which have been used to treat OA with good therapeutic results.This safe,simple,and effective therapy is expected to be applied and promoted in the future.In this paper,the detailed pathogenesis,diagnosis,and current clinical treatments for OA are introduced.Then,clinical studies and the therapeutic mechanism of SVF for the treatment of OA are summarized.

关键词： Arthritis Articular cartilage stromal vascular fraction Mesenchymal stem cells Cell therapy

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Advancements in adipose-derived stem cell therapy for skin fibrosis

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World Journal of Stem Cells 2023年第5期15卷 342-353页

作者： Yu-Xin Liu Jia-Ming Sun Chia-Kang Ho Ya Gao Dong-Sheng Wen Yang-Dan Liu Lu Huang Yi-Fan Zhang Department of Plastic and Reconstructive Surgery Shanghai Ninth People's HospitalShanghai Jiao Tong UniversityShanghai 200011China

Pathological scarring and scleroderma,which are the most common conditions of skin fibrosis,pathologically manifest as fibroblast proliferation and extracellular matrix(ECM)hyperplasia.Fibroblast proliferation and ECM hyperplasia lead to fibrotic tissue remodeling,causing an exaggerated and prolonged wound-healing response.The pathogenesis of these diseases has not been fully clarified and is unfortunately accompanied by exceptionally high medical needs and poor treatment effects.Currently,a promising and relatively low-cost treatment has emerged-adipose-derived stem cell(ASC)therapy as a branch of stem cell therapy,including ASCs and their derivatives-purified ASC,stromal vascular fraction,ASC-conditioned medium,ASC exosomes,etc.,which are rich in sources and easy to obtain.ASCs have been widely used in therapeutic settings for patients,primarily for the defection of soft tissues,such as breast enhancement and facial contouring.In the field of skin regeneration,ASC therapy has become a hot research topic because it is beneficial for reversing skin fibrosis.The ability of ASCs to control profibrotic factors as well as anti-inflammatory and immunomodulatory actions will be discussed in this review,as well as their new applications in the treatment of skin fibrosis.Although the long-term effect of ASC therapy is still unclear,ASCs have emerged as one of the most promising systemic antifibrotic therapies under development.

关键词： Adipose-derived stem cell Cicatrix,hypertrophic Keloid Scleroderma,localized stromal vascular fraction Exosomes

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