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.Mos...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.展开更多
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, viabil...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.展开更多
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 enzy...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 medicine.展开更多
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 rese...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 powered,multi-center,double-blinded,randomised clinical trials with longer follow-ups are needed to further establish safety and justify its clinical use.展开更多
In regenerative medicine,the isolation of mesenchymal stromal cells(MSCs)from the adipose tissue’s stromal vascular fraction(SVF)is a critical area of study.Our review meticulously examines the isolation process of M...In regenerative medicine,the isolation of mesenchymal stromal cells(MSCs)from the adipose tissue’s stromal vascular fraction(SVF)is a critical area of study.Our review meticulously examines the isolation process of MSCs,starting with the extraction of adipose tissue.The choice of liposuction technique,anatomical site,and immediate processing are essential to maintain cell functionality.We delve into the intricacies of enzymatic digestion,emphasizing the fine-tuning of enzyme concentrations to maximize cell yield while preventing harm.The review then outlines the filtration and centrifugation techniques necessary for isolating a purified SVF,alongside cell viability assessments like flow cytometry,which are vital for confirming the efficacy of the isolated MSCs.We discuss the advantages and drawbacks of using autologous vs allogeneic SVF sources,touching upon immunocompatibility and logistical considerations,as well as the variability inherent in donor-derived cells.Anesthesia choices,the selection between hypo-dermic needles vs liposuction cannulas,and the role of adipose tissue lysers in achieving cellular dissociation are evaluated for their impact on SVF isolation.Centrifugation protocols are also analyzed for their part in ensuring the integrity of the SVF.The necessity for standardized MSC isolation protocols is highlighted,promoting reproducibility and successful clinical application.We encourage ongoing research to deepen the understanding of MSC biology and therapeutic action,aiming to further the field of regenerative medicine.The review concludes with a call for rigorous research,interdisciplinary collaboration,and strict adherence to ethical and regulatory standards to safeguard patient safety and optimize treatment outcomes with MSCs.展开更多
Recently,we read a mini-review published by Jeyaraman et al.The article explored the optimal methods for isolating mesenchymal stromal cells from adipose tissue-derived stromal vascular fraction(SVF).Key factors inclu...Recently,we read a mini-review published by Jeyaraman et al.The article explored the optimal methods for isolating mesenchymal stromal cells from adipose tissue-derived stromal vascular fraction(SVF).Key factors include tissue source,processing techniques,cell viability assessment,and the advantages/disadvantages of autologous vs allogeneic use.The authors emphasized the need for standardized protocols for SVF isolation,ethical and regulatory standards for cell-based therapy,and safety to advance mesenchymal stromal cell-based therapies in human patients.This manuscript shares our perspective on SVF isolation in canines.We discussed future directions to potentiate effective regenerative medicine therapeutics in human and veterinary medicine.展开更多
Background:The stromal vascular fraction(SVF),a cluster of stem and progenitor cells isolated from adipose tissue,holds significant promise for application in regenerative medicine.However,the existing methods for SVF...Background:The stromal vascular fraction(SVF),a cluster of stem and progenitor cells isolated from adipose tissue,holds significant promise for application in regenerative medicine.However,the existing methods for SVF isolation are time-consuming and expensive.Thus,in this study,we explored a new method of SVF extrac-tion-ultrasound-assisted SVF isolation(USASI)-and compared the viability and characteristics of SVF isolated using different methods.Methods:SVF extraction methods using different combinations of ultrasound power,ultrasound time,collagenase dosage,and collagenase digestion time were compared with those of the control group(collagenase digestion method).The cell yield and vitality of the SVF were evaluated via cell counting and trypan blue staining.The cell components and immunophenotypes of freshly isolated SVF were analyzed using flow cytometry.The prolifer-ative capacity and differentiation potential of the SVF were also identified.Results:Ultrasonication at 95 W-20 kHz for 30 s followed by digestion with 0.15%collagenase for 30 min was identified as the most suitable parameter for the USASI method in isolating SVF,as recommended based on the evaluation of various tested conditions.The USASI method significantly reduced the collagenase dosage and shortened the digestion time.Compared to the collagenase digestion method,the USASI method had a higher cell yield and cell viability,with no adverse effects on cell components,proliferative capacity,or multipotential differentiation capacity.Conclusion:With reduced processing time,lower collagenase dosage,and increased cell yield without impairing the viability and characteristics of SVF,USASI holds the potential to emerge as a time-saving and cost-effective method for future clinical applications.展开更多
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...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.展开更多
In this editorial,we comment on the paper by Muthu et al published in the recent issue of the journal.This editorial review focusses on the use of adipose-derived stem cells(ADSCs)in knee osteoarthritis treatment.We d...In this editorial,we comment on the paper by Muthu et al published in the recent issue of the journal.This editorial review focusses on the use of adipose-derived stem cells(ADSCs)in knee osteoarthritis treatment.We discuss the differences between the stromal vascular fraction and microfragmented adipose tissue and highlight the results of clinical studies comparing both treatments and the use of hyaluronic acid,platelet-rich plasma,and bone marrow aspirate concentrate.The use of expanded ADSCs is also discussed;moreover,concerns regarding treatment with ADSCs,particularly the heterogeneity of published studies and the need to standardize protocols to explore clinical potential is explored.展开更多
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 ...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 comparative study was conducted to evaluate the effectiveness and safety of the Lipocube Hybrid SVF, which has shown promise in laboratory settings, for different stages of osteoarthritis. The study findings provide valuable insights into the potential of Lipocube Hybrid SVF as a regenerative therapy for OA, highlighting its suitability for addressing this debilitating condition.展开更多
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...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.展开更多
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 20...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.展开更多
Objective To investigate the effect of adipose stromal vascular fraction cells(SVFs)on the survival rate of fat ransplantation.Methods 0.5mL autologous fat tissue was mixed with: ① DiI-labeled autologous SVFs (Group ...Objective To investigate the effect of adipose stromal vascular fraction cells(SVFs)on the survival rate of fat ransplantation.Methods 0.5mL autologous fat tissue was mixed with: ① DiI-labeled autologous SVFs (Group A);②展开更多
Adipose-derived stem cells(ADSCs)residing in the stromal vascular fraction(SVF)of white adipose tissue are recently emerging as an alternative tool for stem cell-based therapy in systemic sclerosis(SSc),a complex conn...Adipose-derived stem cells(ADSCs)residing in the stromal vascular fraction(SVF)of white adipose tissue are recently emerging as an alternative tool for stem cell-based therapy in systemic sclerosis(SSc),a complex connective tissue disorder affecting the skin and internal organs with fibrotic and vascular lesions.Several preclinical and clinical studies have reported promising therapeutic effects of fat grafting and autologous SVF/ADSC-based local treatment for facial and hand cutaneous manifestations of SSc patients.However,currently available data indicate that ADSCs may represent a double-edged sword in SSc,as they may exhibit a pro-fibrotic and anti-adipogenic phenotype,possibly behaving as an additional pathogenic source of pro-fibrotic myofibroblasts through the adipocyte-to-myofibroblast transition process.Thus,in the perspective of a larger employ of SSc-ADSCs for further therapeutic applications,it is important to definitely unravel whether these cells present a comparable phenotype and similar immunosuppressive,anti-inflammatory,anti-fibrotic and pro-angiogenic properties in respect to healthy ADSCs.In light of the dual role that ADSCs seem to play in SSc,this review will provide a summary of the most recent insights into the preclinical and clinical studies employing SVF and ADSCs for the treatment of the disease and,at the same time,will focus on the main findings highlighting the possible involvement of these stem cells in SSc-related fibrosis pathogenesis.展开更多
The use of adipose-derived cells as a treatment for a variety of diseases is becoming increasingly common. These therapies include the use of cultured mesenchymal stem cells (MSCs) and freshly isolated stromal vascula...The use of adipose-derived cells as a treatment for a variety of diseases is becoming increasingly common. These therapies include the use of cultured mesenchymal stem cells (MSCs) and freshly isolated stromal vascular fraction (SVF) alone, or in conjunction with other cells such as adipocytes. There is a substantial amount of literature published on the therapeutic properties of MSCs and their secretions as the main driver of their therapeutic effect. However, there is little data available on the therapeutic potential of secretions from SVF, either with or without adipocytes. We investigated the ability of secretions from human adipose SVF alone and the SVF co-cultured with adipocytes as a proxy for cell therapy, to ameliorate an inflammatory disorder. This ethics approved study involved the treatment of collagen antibody-induced arthritis (CAIA) in mice with secretions from SVF, SVF co-cultured with adipocytes, or a vehicle control via both intravenous (IV) and intramuscular (IM) routes. Treatment outcome was assessed by paw volume, ankle size and clinical arthritis score measurements. Serum samples were obtained following euthanasia and analysed for a panel of 32 mouse cytokines and growth factors. The dose and timing regime used for the IM administration of both human secretion mixtures did not significantly ameliorate arthritis in this model. The IV administration of SVF adipocyte co-culture secretions reduced the paw volume, and significantly reduced the ankle size and clinical arthritis score when compared to the IV vehicle control mice. This was a superior therapeutic effect than treatment with SVF secretions. Furthermore, treatment with SVF adipocyte coculture secretions resulted in a significant reduction in serum levels of key cytokines, IL-2 and VEGF, involved in the pathogenesis of rheumatoid arthritis. Therefore, the SVF cocultured with adipocytes is an attractive therapeutic for inflammatory conditions.展开更多
BACKGROUND Esophageal perforation or postoperative leak after esophageal surgery remain a life-threatening condition.The optimal management strategy is still unclear.AIM To determine clinical outcomes and complication...BACKGROUND Esophageal perforation or postoperative leak after esophageal surgery remain a life-threatening condition.The optimal management strategy is still unclear.AIM To determine clinical outcomes and complications of our 15-year experience in the multidisciplinary management of esophageal perforations and anastomotic leaks.METHODS A retrospective single-center observational study was performed on 60 patients admitted at our department for esophageal perforations or treated for an anastomotic leak developed after esophageal surgery from January 2008 to December 2023.Clinical outcomes were analyzed,and complications were evaluated to investigate the efficacy and safety of our multidisciplinary management based on the preservation of the native or reconstructed esophagus,when feasible.RESULTS Among the whole series of 60 patients,an urgent surgery was required in 8 cases due to a septic state.Fifty-six patients were managed by endoscopic or hybrid treatments,obtaining the resolution of the esophageal leak/perforation without removal of the native or reconstructed esophagus.The mean time to resolution was 54.95±52.64 days,with a median of 35.5 days.No severe complications were recorded.Ten patients out of 56(17.9%)developed pneumonia that was treated by specific antibiotic therapy,and in 6 cases(10.7%)an atrial fibrillation was recorded.Seven patients(12.5%)developed a stricture within 12 months,requiring one or two endoscopic pneumatic dilations to solve the problem.Mortality was 1.7%.CONCLUSION A proper multidisciplinary approach with the choice of the most appropriate treatment can be the key for success in managing esophageal leaks or perforations and preserving the esophagus.展开更多
基金Supported by National Natural Science Foundation of China,No.82070801,No.82100858,No.82073227China Postdoctoral Science Foundation,No.2020M671661+1 种基金Jiangsu Province Science Foundation for Youths,No.BK20200569Jiangsu Province Research Founding for Postdoctoral,No.1412000016.
文摘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.
文摘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.
文摘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 medicine.
文摘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 powered,multi-center,double-blinded,randomised clinical trials with longer follow-ups are needed to further establish safety and justify its clinical use.
文摘In regenerative medicine,the isolation of mesenchymal stromal cells(MSCs)from the adipose tissue’s stromal vascular fraction(SVF)is a critical area of study.Our review meticulously examines the isolation process of MSCs,starting with the extraction of adipose tissue.The choice of liposuction technique,anatomical site,and immediate processing are essential to maintain cell functionality.We delve into the intricacies of enzymatic digestion,emphasizing the fine-tuning of enzyme concentrations to maximize cell yield while preventing harm.The review then outlines the filtration and centrifugation techniques necessary for isolating a purified SVF,alongside cell viability assessments like flow cytometry,which are vital for confirming the efficacy of the isolated MSCs.We discuss the advantages and drawbacks of using autologous vs allogeneic SVF sources,touching upon immunocompatibility and logistical considerations,as well as the variability inherent in donor-derived cells.Anesthesia choices,the selection between hypo-dermic needles vs liposuction cannulas,and the role of adipose tissue lysers in achieving cellular dissociation are evaluated for their impact on SVF isolation.Centrifugation protocols are also analyzed for their part in ensuring the integrity of the SVF.The necessity for standardized MSC isolation protocols is highlighted,promoting reproducibility and successful clinical application.We encourage ongoing research to deepen the understanding of MSC biology and therapeutic action,aiming to further the field of regenerative medicine.The review concludes with a call for rigorous research,interdisciplinary collaboration,and strict adherence to ethical and regulatory standards to safeguard patient safety and optimize treatment outcomes with MSCs.
基金Supported by the Department of Biotechnology,Ministry of Science and Technology,Government of India,New Delhi,No.BT/PR42179/AAQ/1/814/2021SERB-State University Research Excellence,No.SUR/2022/001952.
文摘Recently,we read a mini-review published by Jeyaraman et al.The article explored the optimal methods for isolating mesenchymal stromal cells from adipose tissue-derived stromal vascular fraction(SVF).Key factors include tissue source,processing techniques,cell viability assessment,and the advantages/disadvantages of autologous vs allogeneic use.The authors emphasized the need for standardized protocols for SVF isolation,ethical and regulatory standards for cell-based therapy,and safety to advance mesenchymal stromal cell-based therapies in human patients.This manuscript shares our perspective on SVF isolation in canines.We discussed future directions to potentiate effective regenerative medicine therapeutics in human and veterinary medicine.
基金supported by the National Natural Science Foundation of China(grant nos.81971848 and 82272287)Shanghai Municipal Key Clinical Specialty(grant no,shslczdzk00901)+2 种基金Clinical Research Plan of SHDC(rant nos.SHDC2020CR1019B and SHC2020CR402)Innovative Research Team of High-Level Local Universities in Shanghai(grant no.SSMU-ZDCX20180700)Shanghai Clinical Research Center of Plastic and Reconstructive Surgery supported by the Science and Technology Commission of Shanghai Municipality(grant no.22MC1940300).
文摘Background:The stromal vascular fraction(SVF),a cluster of stem and progenitor cells isolated from adipose tissue,holds significant promise for application in regenerative medicine.However,the existing methods for SVF isolation are time-consuming and expensive.Thus,in this study,we explored a new method of SVF extrac-tion-ultrasound-assisted SVF isolation(USASI)-and compared the viability and characteristics of SVF isolated using different methods.Methods:SVF extraction methods using different combinations of ultrasound power,ultrasound time,collagenase dosage,and collagenase digestion time were compared with those of the control group(collagenase digestion method).The cell yield and vitality of the SVF were evaluated via cell counting and trypan blue staining.The cell components and immunophenotypes of freshly isolated SVF were analyzed using flow cytometry.The prolifer-ative capacity and differentiation potential of the SVF were also identified.Results:Ultrasonication at 95 W-20 kHz for 30 s followed by digestion with 0.15%collagenase for 30 min was identified as the most suitable parameter for the USASI method in isolating SVF,as recommended based on the evaluation of various tested conditions.The USASI method significantly reduced the collagenase dosage and shortened the digestion time.Compared to the collagenase digestion method,the USASI method had a higher cell yield and cell viability,with no adverse effects on cell components,proliferative capacity,or multipotential differentiation capacity.Conclusion:With reduced processing time,lower collagenase dosage,and increased cell yield without impairing the viability and characteristics of SVF,USASI holds the potential to emerge as a time-saving and cost-effective method for future clinical applications.
文摘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.
文摘In this editorial,we comment on the paper by Muthu et al published in the recent issue of the journal.This editorial review focusses on the use of adipose-derived stem cells(ADSCs)in knee osteoarthritis treatment.We discuss the differences between the stromal vascular fraction and microfragmented adipose tissue and highlight the results of clinical studies comparing both treatments and the use of hyaluronic acid,platelet-rich plasma,and bone marrow aspirate concentrate.The use of expanded ADSCs is also discussed;moreover,concerns regarding treatment with ADSCs,particularly the heterogeneity of published studies and the need to standardize protocols to explore clinical potential is explored.
文摘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 comparative study was conducted to evaluate the effectiveness and safety of the Lipocube Hybrid SVF, which has shown promise in laboratory settings, for different stages of osteoarthritis. The study findings provide valuable insights into the potential of Lipocube Hybrid SVF as a regenerative therapy for OA, highlighting its suitability for addressing this debilitating condition.
基金Supported by National Natural Science Foundation of China,No.81772103 and No.82172234Shanghai Clinical Research Center of Plastic and Reconstructive Surgery supported by Science and Technology Commission of Shanghai Municipality,China,No.22MC1940300。
文摘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.
文摘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.
文摘Objective To investigate the effect of adipose stromal vascular fraction cells(SVFs)on the survival rate of fat ransplantation.Methods 0.5mL autologous fat tissue was mixed with: ① DiI-labeled autologous SVFs (Group A);②
文摘Adipose-derived stem cells(ADSCs)residing in the stromal vascular fraction(SVF)of white adipose tissue are recently emerging as an alternative tool for stem cell-based therapy in systemic sclerosis(SSc),a complex connective tissue disorder affecting the skin and internal organs with fibrotic and vascular lesions.Several preclinical and clinical studies have reported promising therapeutic effects of fat grafting and autologous SVF/ADSC-based local treatment for facial and hand cutaneous manifestations of SSc patients.However,currently available data indicate that ADSCs may represent a double-edged sword in SSc,as they may exhibit a pro-fibrotic and anti-adipogenic phenotype,possibly behaving as an additional pathogenic source of pro-fibrotic myofibroblasts through the adipocyte-to-myofibroblast transition process.Thus,in the perspective of a larger employ of SSc-ADSCs for further therapeutic applications,it is important to definitely unravel whether these cells present a comparable phenotype and similar immunosuppressive,anti-inflammatory,anti-fibrotic and pro-angiogenic properties in respect to healthy ADSCs.In light of the dual role that ADSCs seem to play in SSc,this review will provide a summary of the most recent insights into the preclinical and clinical studies employing SVF and ADSCs for the treatment of the disease and,at the same time,will focus on the main findings highlighting the possible involvement of these stem cells in SSc-related fibrosis pathogenesis.
文摘The use of adipose-derived cells as a treatment for a variety of diseases is becoming increasingly common. These therapies include the use of cultured mesenchymal stem cells (MSCs) and freshly isolated stromal vascular fraction (SVF) alone, or in conjunction with other cells such as adipocytes. There is a substantial amount of literature published on the therapeutic properties of MSCs and their secretions as the main driver of their therapeutic effect. However, there is little data available on the therapeutic potential of secretions from SVF, either with or without adipocytes. We investigated the ability of secretions from human adipose SVF alone and the SVF co-cultured with adipocytes as a proxy for cell therapy, to ameliorate an inflammatory disorder. This ethics approved study involved the treatment of collagen antibody-induced arthritis (CAIA) in mice with secretions from SVF, SVF co-cultured with adipocytes, or a vehicle control via both intravenous (IV) and intramuscular (IM) routes. Treatment outcome was assessed by paw volume, ankle size and clinical arthritis score measurements. Serum samples were obtained following euthanasia and analysed for a panel of 32 mouse cytokines and growth factors. The dose and timing regime used for the IM administration of both human secretion mixtures did not significantly ameliorate arthritis in this model. The IV administration of SVF adipocyte co-culture secretions reduced the paw volume, and significantly reduced the ankle size and clinical arthritis score when compared to the IV vehicle control mice. This was a superior therapeutic effect than treatment with SVF secretions. Furthermore, treatment with SVF adipocyte coculture secretions resulted in a significant reduction in serum levels of key cytokines, IL-2 and VEGF, involved in the pathogenesis of rheumatoid arthritis. Therefore, the SVF cocultured with adipocytes is an attractive therapeutic for inflammatory conditions.
文摘BACKGROUND Esophageal perforation or postoperative leak after esophageal surgery remain a life-threatening condition.The optimal management strategy is still unclear.AIM To determine clinical outcomes and complications of our 15-year experience in the multidisciplinary management of esophageal perforations and anastomotic leaks.METHODS A retrospective single-center observational study was performed on 60 patients admitted at our department for esophageal perforations or treated for an anastomotic leak developed after esophageal surgery from January 2008 to December 2023.Clinical outcomes were analyzed,and complications were evaluated to investigate the efficacy and safety of our multidisciplinary management based on the preservation of the native or reconstructed esophagus,when feasible.RESULTS Among the whole series of 60 patients,an urgent surgery was required in 8 cases due to a septic state.Fifty-six patients were managed by endoscopic or hybrid treatments,obtaining the resolution of the esophageal leak/perforation without removal of the native or reconstructed esophagus.The mean time to resolution was 54.95±52.64 days,with a median of 35.5 days.No severe complications were recorded.Ten patients out of 56(17.9%)developed pneumonia that was treated by specific antibiotic therapy,and in 6 cases(10.7%)an atrial fibrillation was recorded.Seven patients(12.5%)developed a stricture within 12 months,requiring one or two endoscopic pneumatic dilations to solve the problem.Mortality was 1.7%.CONCLUSION A proper multidisciplinary approach with the choice of the most appropriate treatment can be the key for success in managing esophageal leaks or perforations and preserving the esophagus.
