Adipose-derived Stromal Vascular Fraction Research Articles

Therapeutic effect of adipose stromal vascular fraction spheroids for partial bladder outlet obstruction induced underactive bladder

BackgroundUnderactive bladder (UAB) is a common clinical problem but related research is rarely explored. As there are currently no effective therapies, the administration of adipose stromal vascular fraction (ad-SVF) provides a new potential method to treat underactive bladder.MethodsMale Sprague–Dawley rats were induced by partial bladder outlet obstruction (PBOO) for four weeks and randomly divided into three groups: rats treated with PBS (Sham group); rats administrated with ad-SVF (ad-SVF group) and rats performed with ad-SVF spheroids (ad-SVFsp group). After four weeks, urodynamic studies were performed to evaluate bladder functions and all rats were sacrificed for further studies.ResultsWe observed that the bladder functions and symptoms of UAB were significantly improved in the ad-SVFsp group than that in the Sham group and ad-SVF group. Meanwhile, our data showed that ad-SVF spheroids could remarkably promote angiogenesis, suppress cell apoptosis and stimulate cell proliferation in bladder tissue than that in the other two groups. Moreover, ad-SVF spheroids increased the expression levels of bFGF, HGF and VEGF-A than ad-SVF. IVIS Spectrum small-animal in vivo imaging system revealed that ad-SVF spheroids could increase the retention rate of transplanted cells in bladder tissue.ConclusionsAd-SVF spheroids improved functions and symptoms of bladder induced by PBOO, which contributes to promote angiogenesis, suppress cell apoptosis and stimulate cell proliferation. Ad-SVF spheroids provide a potential treatment for the future patients with UAB.

The Effect of Autologous Adipose-Derived Stromal Vascular Fractions on Cartilage Regeneration Was Quantitatively Evaluated Based on the 3D-FS-SPGR Sequence: A Clinical Trial Study.

Background Numerous reports confirmed the safety and clinical efficacy of autologous adipose-derived stromal vascular fractions (SVF), which have recently been used to treat osteoarthritis (OA). However, there is still no consensus as to whether SVF can promote cartilage regeneration. Herein, the purpose of our study was to evaluate the effectiveness of SVF versus hyaluronic acid (HA) in cartilage regeneration by establishing a cartilage model based on the three-dimensional fat-suppressed spoiled gradient recalled echo (3D-FS-SPGR) sequence. Methods Patients with symptomatic OA were recruited in our research, who were randomized into two groups. Meanwhile, patients in Kellgren-Lawrence (K-L) grades 2 and 3 were distinguished in each group. In the test group, patients received SVF injections of the knee, while patients in the control group received the same dose of HA. Each patient underwent the 3D-FS-SPGR sequence to establish a cartilage model at baseline, 6 months, and 12 months, respectively. The cartilage was characterized into six regions, and relevant parameters of the cartilage model were counted. Clinical and radiographic scores were recorded in one-year follow-up. Results In all regions, the thickness and volume of cartilage defect and the volume of healthy cartilage were improved to some extent in the test group, especially the medial femoral condyle (MF) and medial tibial condyle (MT). In grades 2 and 3, the thickness and volume of cartilage defect decreased by 0.92 ± 0.18 mm and 1.03 ± 0.23 mm and 84.00 ± 32.30 mm3 and 130.30 ± 49.56 mm3 in MF and by 0.96 ± 0.22 mm and 0.99 ± 0.14 mm and 64.18 ± 21.40 mm3 and 95.11 ± 19.93 mm3 in MT, respectively. No such phenomenon was observed in the control group. Meanwhile, the SVF-treated knees showed significant improvement in clinical and radiographic scores at 12 months. Nevertheless, these scores of the control group became worse at 12-month follow-up visit. Conclusion Taken together, this study shows that intra-articular injection of SVF markedly improved the clinical symptoms without adverse events, thereby repairing the damaged articular cartilage through cartilage regeneration.

Intra-articular Injection of Autologous Adipose-Derived Stem Cells or Stromal Vascular Fractions: Are They Effective for Patients With Knee Osteoarthritis? A Systematic Review With Meta-analysis of Randomized Controlled Trials

Background: Intra-articular injection of adipose-derived stem cells, which are divided into adipose-derived mesenchymal stem cells (ASCs) and adipose-derived stromal vascular fractions (ADSVFs), has been reported to be a viable treatment modality for knee osteoarthritis (OA); however, its efficacy remains limited. Purpose: This study aimed to provide comprehensive information about the efficacy and safety of intra-articular injections of autologous ASCs and ADSVFs without adjuvant treatment in patients with knee OA. Study Design: Meta-analysis; Level of evidence, 1. Methods: A systematic search of the MEDLINE, Embase, Web of Science, and Cochrane Library databases was performed to identify randomized controlled trials (RCTs) that evaluated the efficacy and safety of intra-articular injections of autologous ASCs or ADSVFs without adjuvant treatments compared with placebo or hyaluronic acid in patients with knee OA. Clinically, the 100-mm visual analog scale for pain relief and the Western Ontario and McMaster Universities Osteoarthritis Index for functional improvement were implemented. Radiologically, cartilage status was assessed using magnetic resonance imaging (MRI). Procedure-related knee pain, swelling, and adverse events (AEs) were evaluated for safety. Additionally, we performed subgroup analyses comparing ASCs versus ADSVFs. Methodological quality was assessed using the modified Coleman Methodology Score (mCMS). Results: A total of 5 RCTs were included in this study. Based on the meta-analysis, ASCs or ADSVFs showed significantly better pain relief at 6 months (Z = 7.62; P < .0001) and 12 months (Z = 7.21; P < .0001) and functional improvement at 6 months (Z = 4.13; P < .0001) and 12 months (Z = 3.79; P = .0002), without a difference in procedure-related knee pain or swelling compared with controls. Although a meta-analysis with regard to cartilage improvements was not performed owing to heterogeneous MRI assessment, 3 studies reported significantly improved cartilage status after the injection. No serious AEs associated with ASCs or ADSVFs were reported. Subgroup analyses showed similar efficacy between ASC and ADSVF treatments. The median mCMS was 70 (range, 55-75). Conclusion: For patients with knee OA, intra-articular injection of autologous ASCs or ADSVFs without adjuvant treatment showed remarkable clinical efficacy and safety at short-term follow-up. Some degree of efficacy has been shown for cartilage regeneration in knee OA, although the evidence remains limited. Further RCTs that directly compare ASCs and ADSVFs are needed.

Effect of Stromal Vascular Fractions on Angiogenesis of Injected Diced Cartilage.

Objectives:This study explored the effect of adipose-derived stromal vascular fractions (SVFs) on angiogenesis in injected autologous diced cartilage.Methods:Stromal vascular fractions were extracted by enzymatic digestion. Cartilage grafts were harvested from 1 side of the auricular cartilage of New Zealand rabbit and then diced to a size of 1.0 mm3. The grafts were divided into 2 groups. The control group was diced cartilage mixed with culture medium, and the experimental group was diced cartilage mixed with SVFs. The 2 groups of composite grafts were subcutaneously implanted on both sides of the back of each rabbit. After 4, 12 and 24 weeks, the tissue structure, number of blood vessels, and angiogenic factors in the grafts were observed.Results:The SVFs conformed to the current standard of the biological evaluation. Under an inverted microscope, the number of layers of chondrocytes in the experimental group was higher than that in the control group at 4 weeks. A small number of inflammatory cells and blood vessels were observed around the cartilage grafts. At 12 and 24 weeks, the volume of tissue was increased gradually by general observation. And a large number of chondrocytes were observed microscopically, whereas the number of inflammatory cells decreased. And meanwhile additional new blood vessels were observed. Immunohistochemical analysis of CD31 showed that the number of capillaries in the control group was significantly lower than that in the experimental group at 4, 12 and 24 weeks. Further, the expression of Hypoxia inducible factor-1 (HIF-1) and vascular endothelial growth factor (VEGF) mRNA and protein were measured by RT-PCR and Western bloting, respectively. The results showed that the mRNA expression of VEGF and HIF-1α in the experimental group was increased. The mRNA level remained higher than that of the control group at 24 weeks (P < 0.05). And the relative expression levels of VEGF and HIF-1α protein in the experimental group were higher than those in the control group at 4, 12 and 24 weeks (P < 0.05).Conclusion:Autologous diced cartilage mixed with adipose-derived SVFs can promote angiogenesis when transplanted by injection. Further research showed that SVFs could increase the expression levels of VEGF and HIF-1α in the grafts, which may be part of the mechanism that SVFs promoted the angiogenesis of diced cartilage.

An Optimized Method for Adipose Stromal Vascular Fraction Isolation and its Application in Fat Grafting.

The stromal vascular fraction (SVF) derived from adipose tissue contains heterogeneous cell populations and has enormous potential for clinical therapy. There are two main methods for SVF isolation: enzymatic isolation and mechanical isolation, both of which have shortcomings. In this study, optimized conditions for the isolation of high-quality SVF were established, and applications in fat grafting were evaluated. Adipose tissue was chopped into small pieces and then ground into an erosive shape using a syringe. The pieces were digested with 0.15% type II collagenase for 35 min at 37°C. After centrifugation, the pellets were resuspended in DMEM and passed through a 100-μm strainer. The filtered cells were analyzed by flow cytometry. The fat graft was enriched with isolated SVF and subcutaneously transplanted into nude mice. Three weeks after transplantation, grafts were isolated, and H&E staining, immunocytochemistry, and western blotting were conducted. The harvested SVF cells reached > 2 × 106/ml of adipose tissue within 90 min of operation. The number of CD34+ ADSCs in our SVF pellets was > 6 × 105/ml of adipose tissue, which has the potential for differentiating into osteoblasts, adipocytes, and chondrocytes. Freshly collected adipose tissue is better for SVF isolation, and isolated SVF should also be kept at 4°C and used as soon as possible. SVF may promote revascularization after fat grafting. The adipose tissue of an SVF co-transplanted group had an integral structure, clear capillaries, and higher VEGF expression. SVF co-transplantation inhibited adipose cell apoptosis. Our study provides an efficient procedure for SVF isolation, its application in fat grafting, and possible underlying mechanisms. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Stromal vascular fraction therapy for knee osteoarthritis: a systematic review.

Background:Regenerative cell therapies, such as adipose-derived stromal vascular fraction (SVF), have been postulated as potential treatments for knee osteoarthritis (KOA).Objectives:To assess the efficacy and safety of SVF treatment against placebo and other standard therapies for treating KOA in adult patients.Design:A systematic review.Data sources and methods:We searched the following databases: MEDLINE via PubMed, Epistemonikos, PEDro, DynaMed, TripDatabase, Elsevier via Clinicalkey and Cochrane Controlled Trials Register. We included prospective interventional studies where treatment with SVF in adults with KOA was compared against placebo or other standard therapies, and results were objectively measured with at least one widely recognised osteoarthritis scale.Results:Among 266 studies published until May 2021, nine met our inclusion criteria. A total of 239 patients (274 knees) were included in our study. The follow-up ranged from 6 to 24 months. Six studies had a control group (only one being placebo). All studies showed that SVF improved pain and functionality measured, in most cases, with the visual analogue scale and the Western Ontario and McMaster Universities Osteoarthritis Index. In addition, five studies reported an improvement in anatomical structures, as detected in MR images. However, the number of cells contained in SVF varied substantially between different studies, which could induce a comparison bias.Conclusion:Although based on a small number of dissimilar studies, SVF was considered a safe treatment for KOA and could be promising in terms of pain, functionality and anatomical structure improvement. However, SVF products need to be standardised, the number of cells homogenised and the use of concomitant treatments reduced to establish proper comparisons.Registration:PROSPERO registration number: CRD42021284187.

Role of adipose tissue grafting and adipose-derived stem cells in peripheral nerve surgery.

The application of autologous fat grafting in reconstructive surgery is commonly used to improve functional form. This review aims to provide an overview of the scientific evidence on the biology of adipose tissue, the role of adipose-derived stem cells, and the indications of adipose tissue grafting in peripheral nerve surgery. Adipose tissue is easily accessible through the lower abdomen and inner thighs. Non-vascularized adipose tissue grafting does not support oxidative and ischemic stress, resulting in variable survival of adipocytes within the first 24 hours. Enrichment of adipose tissue with a stromal vascular fraction is purported to increase the number of adipose-derived stem cells and is postulated to augment the long-term stability of adipose tissue grafts. Basic science nerve research suggests an increase in nerve regeneration and nerve revascularization, and a decrease in nerve fibrosis after the addition of adipose-derived stem cells or adipose tissue. In clinical studies, the use of autologous lipofilling is mostly applied to secondary carpal tunnel release revisions with promising results. Since the use of adipose-derived stem cells in peripheral nerve reconstruction is relatively new, more studies are needed to explore safety and long-term effects on peripheral nerve regeneration. The Food and Drug Administration stipulates that adipose-derived stem cell transplantation should be minimally manipulated, enzyme-free, and used in the same surgical procedure, e.g. adipose tissue grafts that contain native adipose-derived stem cells or stromal vascular fraction. Future research may be shifted towards the use of tissue-engineered adipose tissue to create a supportive microenvironment for autologous graft survival. Shelf-ready alternatives could be enhanced with adipose-derived stem cells or growth factors and eliminate the need for adipose tissue harvest.

Technique for Obtaining Mesenchymal Stem Cell from Adipose Tissue and Stromal Vascular Fraction Characterization in Long-Term Cryopreservation.

Human mesenchymal stem cells derived from adipose tissue have become increasingly attractive as they show appropriate features and are an accessible source for regenerative clinical applications. Different protocols have been used to obtain adipose-derived stem cells. This article describes different steps of an improved time-saving protocol to obtain a more significant amount of ADSC, showing how to cryopreserve and thaw ADSC to obtain viable cells for culture expansion. One hundred milliliters of lipoaspirate were collected, using a 26 cm three-hole and 3 mm caliber syringe liposuction, from the abdominal area of nine patients who subsequently underwent elective abdominoplasty. The stem cells isolation was carried out with a series of washes with Dulbecco's Phosphate Buffered Saline (DPBS) solution supplemented with calcium and the use of collagenase. Stromal Vascular Fraction (SVF) cells were cryopreserved, and their viability was checked by immunophenotyping. The SVF cellular yield was 15.7 x 105 cells/mL, ranging between 6.1-26.2 cells/mL. Adherent SVF cells reached confluence after an average of 7.5 (±4.5) days, with an average cellular yield of 12.3 (± 5.7) x 105 cells/mL. The viability of thawed SVF after 8 months, 1 year, and 2 years ranged between 23.06%-72.34% with an average of 47.7% (±24.64) with the lowest viability correlating with cases of two-year freezing. The use of DPBS solution supplemented with calcium and bag resting times for fat precipitation with a shorter time of collagenase digestion resulted in an increased stem cell final cellular yield. The detailed procedure for obtaining high yields of viable stem cells was more efficient regarding time and cellular yield than the techniques from previous studies. Even after a long period of cryopreservation, viable ADSC cells were found in the SVF.

Technique for Obtaining Mesenchymal Stem Cell from Adipose Tissue and Stromal Vascular Fraction Characterization in Long-Term Cryopreservation

Technique for Obtaining Mesenchymal Stem Cell from Adipose Tissue and Stromal Vascular Fraction Characterization in Long-Term Cryopreservation

Sodium salicylate rewires hepatic metabolic pathways in obesity and attenuates IL-1β secretion from adipose tissue: The implications for obesity-impaired reverse cholesterol transport

IntroductionHigh-fat diet (HFD)-induced obesity impairs clearance of cholesterol through the Reverse Cholesterol Transport (RCT) pathway, with downregulation in hepatic expression of cholesterol and bile acid transporters, namely ABCG5/8 and ABCB11, and reduced high-density lipoprotein (HDL) cholesterol efflux capacity (CEC). In the current study, we hypothesized that the development of hepatosteatosis, secondary to adipose-tissue dysfunction, contributes to obesity-impaired RCT and that such effects could be mitigated using the anti-inflammatory drug sodium salicylate (NaS). Materials and methodsC57BL/6J mice, fed HFD ± NaS or low-fat diet (LFD) for 24 weeks, underwent glucose and insulin tolerance testing. The 3H-cholesterol movement from macrophage-to-feces was assessed in vivo. HDL-CEC was determined ex vivo. Cytokine secretion from adipose-derived stromal vascular fraction (SVF) cells was measured ex vivo. Liver and HDL proteins were determined by mass spectrometry and analyzed using Ingenuity Pathway Analysis. ResultsNaS delayed HFD-induced weight gain, abrogated priming of pro-IL-1β in SVFs, attenuated insulin resistance, and prevented steatohepatitis (ectopic fat accumulation in the liver). Prevention of hepatosteatosis coincided with increased expression of PPAR-alpha/beta-oxidation proteins with NaS and reduced expression of LXR/RXR-induced proteins including apolipoproteins. The latter effects were mirrored within the HDL proteome in circulation. Despite remarkable protection shown against steatosis, HFD-induced hypercholesterolemia and repression of the liver-to-bile cholesterol transporter, ABCG5/8, could not be rescued with NaS. Discussions and conclusionsThe cardiometabolic health benefits of NaS may be attributed to the reprogramming of hepatic metabolic pathways to increase fatty acid utilization in the settings of nutritional overabundance. Reduced hepatic cholesterol levels, coupled with reduced LXR/RXR-induced proteins, may underlie the lack of rescue of ABCG5/8 expression with NaS. This remarkable protection against HFD-induced hepatosteatosis did not translate to improvements in cholesterol homeostasis.

Rehabilitation of spinal cord injury with autogenous stromal vascular fraction in dogs

Background: Spinal cord injury (SCI) is an unexpected, traumatic event, its consequences often persist for the rest of life. The neurological deficit caused by spinal cord (SC) injury is permanent, and conservative treatment can not completely restore neurological functions in animals. Repeated autogenous adipose-derived stromal vascular fraction (SVF) has been used to deliver MSCs, growth factors such as brain-derived neurotrophic factor, nerve growth factor, and neurotrophin-3 at the site of injury. Methods: In the present study, six dogs presented with SCI, were routinely examined based on standard neurological examination protocol and subjected to the survey radiography. Treatment plans differed as per the presentation of the case. Stable and physically responsive patients were selected for repeated autogenous SVF therapy for rehabilitation. Results: After conservative treatment in SCI, from the second week onwards, when patient supports or able to move affected area in relation to forequarter, the patients were administered repeated autogenous SVF therapy, which restored motor function in the form of intermittent weight-bearing on fetlock and/or posture change. Significance: Spinal cord damage either partial or complete is always an ailment related to neurological deficit of the affected body parts. The repeated administration of autogenous stromal vascular fraction therapy in combination of physiotherapy significantly reverse, the effects of neurological deficit and progressively restore posture and weight bearing on the affected hind quarter in dogs.

Administration of adipose stromal vascular fraction attenuates acute rejection in donation after circulatory death rat renal transplantation.

Stem cell therapy represents a new approach to induce immune tolerance in solid organ transplantation. However, the time-consuming process of stem cell expending limits the range of stem cell treatment. Uncultured adipose stromal vascular fraction is considered an attractive cell source for cell-based therapy. This study aimed to evaluate the effect of stromal vascular fraction on the immune system in donation after circulatory death rat renal transplantation. Stromal vascular fraction cells and splenocytes were co-cultured to evaluate the effect of stromal vascular fraction on splenocyte proliferation and viability. Sprague-Dawley rats were used as donors. and Wistar rats as recipients to establish a donation after a circulatory death rat renal transplantation model. Warm ischemia time was 5min. Stromal vascular fraction was administered in the rat model following the intra-arterial route. The spleens and grafts of recipients were harvested on days1, 3 and 7 post-transplantation for assessing acute rejection, infiltration of inflammatory cells, indoleamine 2, 3-dioxygenase expression and T-cell frequency in the spleen. Stromal vascular fraction could inhibit proliferation and induce apoptosis of splenocytes invitro (P<0.05). The administration of stromal vascular fraction could significantly reduce acute rejection and infiltration of CD8+ Tcells and mononuclear macrophages in grafts, and increase indoleamine 2, 3-dioxygenase expression (P<0.05). The frequency of CD8+ Tcells decreased, and the frequency of CD25+ Foxp3+ regulatory Tcells increased in the spleen of the acute rejection+stromal vascular fraction group on day 7 post-transplantation (P<0.05). Administration of the adipose stromal vascular fraction could attenuate acute rejection in donation after circulatory death renal transplantation by increasing the ratio of regulatory Tcells and enhancing indoleamine 2, 3-dioxygenase expression.

Abstract 10247: Establishing a Therapeutically Modifiable ROS/RNS-Beta 1 Adrenergic Receptor Desensitization and Internalization Axis in Aging Coronary Microvessels

Introduction: Coronary Microvascular Disease (CMD) causes hyperconstriction, reduced perfusion, and chronic angina in aging. We previously showed increased coronary microvascular ROS and reduced NO/glutathione in aging rats correlating with reduced β1 Adrenergic receptor (β1ADR) dilation. Adipose Stromal Vascular Fraction (SVF) therapy reverses oxidative stress in CMD to improve β1ADR function. Our objective is to elucidate a mechanism for SVF’s recovery of β1ADR function in pursuit of a cell therapy to treat CMD. Hypothesis: β1ADR dilation is reduced in aging due to ROS-mediated receptor desensitization &amp; internalization, reversible by inhibition of GRK2/dynamin &amp; SVF antioxidation. Methods: Rat coronary microvessels were isolated from young (YC, 3-6 months), old (OC, 24 months), and old + SVF injection (OSVF, 24 months). RNAseq (n = 3 per group) and immunofluorescence (n ≥ 5 per group) were used to analyze pro/antioxidant gene &amp; protein expression. Using pressure myography, dilation to isoproterenol was evaluated at baseline and with ROS (hydrogen peroxide and menadione) or RNS (sodium nitroprusside, SNP) +/- inhibitors of receptor desensitization (GRK2 via paroxetine) and internalization (dynamin via dynasore). Significance was set at p &lt; .05 utilizing Two-Way Repeated Measures ANOVA with Holm-Sidak post-hoc analysis. Results: Aging (n = 16) reduced dilation to isoproterenol, reversed to youthful (n = 17) levels by SVF (n = 16). In YC/OSVF, ROS (n = 10 &amp; 6) attenuated dilation reversed by dynasore (n = 8) and paroxetine (n = 7). In OC, SNP (n = 7), dynasore (n = 10), and paroxetine (n = 5) restored dilation. Aging increased prooxidant genetic (xanthine oxidase) and protein (NOX4) expression and increased antioxidant genetic (catalase) but not protein expression. SVF reduced prooxidant genetic (dynamin related protein 1) and protein (NOX4) expression with increased antioxidant genetic (glutathione synthetase) and protein (SOD2) expression. Conclusion: ROS in aging causes β1ADR dysfunction via desensitization &amp; internalization, as their inhibition preserves β1ADR function. We name this interaction the ROS/RNS- β1ADR Desensitization &amp; Internalization Axis , which was therapeutically modulated by SVF antioxidation to restore β1ADR function.

Cell therapy rescues aging-induced beta-1 adrenergic receptor and GRK2 dysfunction in the coronary microcirculation.

Our past study showed that coronary arterioles isolated from adipose-derived stromal vascular fraction (SVF)-treated rats showed amelioration of the age-related decrease in vasodilation to beta-adrenergic receptor (β-AR) agonist and improved β-AR-dependent coronary flow and microvascular function in a model of advanced age. We hypothesized that intravenously (i.v.) injected SVF improves coronary microvascular function in aged rats by re-establishing the equilibrium of the negative regulators of the internal adrenergic signaling cascade, G-protein receptor kinase 2 (GRK2) and G-alpha inhibitory (Gαi) proteins, back to youthful levels. Female Fischer-344 rats aged young (3 months, n = 24), old (24 months, n = 26), and old animals that received 1 × 107 green fluorescent protein (GFP+) SVF cells (O + SVF, n = 11) 4 weeks prior to sacrifice were utilized. Overnight urine was collected prior to sacrifice for catecholamine measurements. Cardiac samples were used for western blotting while coronary arterioles were isolated for pressure myography studies, immunofluorescence staining, and RNA sequencing. Coronary microvascular levels of the β1 adrenergic receptor are decreased with advancing age, but this decreased expression was rescued by SVF treatment. Aging led to a decrease in phosphorylated GRK2 in cardiomyocytes vs. young control with restoration of phosphorylation status by SVF. In vessels, there was no change in genetic transcription (RNAseq) or protein expression (immunofluorescence); however, inhibition of GRK2 (paroxetine) led to improved vasodilation to norepinephrine in the old control (OC) and O + SVF, indicating greater GRK2 functional inhibition of β1-AR in aging. SVF works to improve adrenergic-mediated vasodilation by restoring the β1-AR population and mitigating signal cascade inhibitors to improve vasodilation.

Efficacy and safety of autologous adipose-derived stromal vascular fraction enriched with platelet-rich plasma in flap repair of transsphincteric cryptoglandular fistulas

BackgroundTransanal advancement flap repair of transsphincteric fistulas is a sphincter-preserving procedure, which frequently fails, probably due to ongoing inflammation in the remaining fistula tract. Adipose-derived stromal vascular fraction (SVF) has immunomodulatory properties promoting wound healing and suppressing inflammation. Platelet-rich plasma (PRP) reinforces this biological effect. The aim of this study was to evaluate the efficacy and safety of autologous adipose-derived SVF enriched with PRP in flap repair of transsphincteric cryptoglandular fistulas.MethodsA prospective cohort study was conducted including consecutive patients with transsphincteric cryptoglandular fistula in a tertiary referral center. During flap repair, SVF was obtained by lipoharvesting and mechanical fractionation of adipose tissue and combined with PRP was injected around the internal opening and into the fistulous wall. Endpoints were fistula healing at clinical examination and fistula closure on postoperative magnetic resonance imaging (MRI). Adverse events were documented.ResultsForty-five patients with transsphincteric cryptoglandular fistula were included (29 males, median age 44 years [range 36–53 years]). In the total study population, primary fistula healing was observed in 38 patients (84%). Among the 42 patients with intestinal continuity at time of surgery, primary fistula healing was observed in 35 patients (84%). In one patient, the fistula recurred, resulting in a long-term healing rate of 82%. MRI, performed in 37 patients, revealed complete closure of the fistula tract in 33 (89.2%). In the other patients, the tract was almost completely obliterated by scar tissue. During follow-up, none of these patients showed clinical signs of recurrence. The postoperative course was uneventful, except for three cases; venous thromboembolism in one patient and bleeding under the flap, necessitating intervention in two patients.ConclusionsAddition of autologous SVF enriched with PRP during flap repair is feasible, safe and might improve outcomes in patients with a transsphincteric cryptoglandular fistula.Trial registrationDutch Trial Register, Trial Number: NL8416, https://www.trialregister.nl/

Efficacy of adipose-derived stromal vascular fraction cells in the management of chronic ulcers: a randomized clinical trial.

Background: Cell therapy is a promising method for improving healing in chronic ulcers through delivery of isolated adipose-derived stromal vascular fraction. Objectives: This study investigates the autologous stem cell yield of adipose tissue and its efficacy in chronic ulcers compared with conventional methods. Methods: This study was a randomized controlled trial. After the study design and protocol were established and ethical committee approval was obtained, we enrolled 100 patients divided into study and control groups. In the study group, we performed debridement and autologous stem cell injection every 3weeks. The control group was treated with debridement and conventional dressing. Assessments included clinical and histological parameters. Results: The study group showed improved healing. Conclusion: Using autologous adipose-derived stromal vascular fraction cells is an effective treatment method for chronic ulcers. This study was registered on the Pan-African Clinical Trial Registry and the number of the registry was PACTR201709002519185.

Adipose tissue and adipose secretome in systemic sclerosis.

Adipose tissue is closely associated with systemic sclerosis (SSc)-pathology, both anatomically and functionally. This review focuses on local effects of adipocytes in the context of adipose to mesenchymal transdifferentiation (AMT), effects of the adipose stromal vascular fraction on SSc pathogenesis and systemic effects of adipose tissue secretome. Novel populations of fibroblasts evolving from adipose tissue were identified- for example COL11+ cancer-associated fibroblasts differentiated from adipose-derived stromal cells. Lipofibroblasts in human lungs were described using nonconventional markers that allow more effective population identification. These findings could make an important contribution to further clarification of adipocyte involvement in SSc.Recent studies confirmed that lipolysis contributes to fibrogenesis through AMT differentiation and release of fatty acids (FA). Unbalanced metabolism of FA has been reported in several studies in SSc. Other adipose tissue secretome molecules (e.g. lysophosphatidic acid), novel adipokines and extracellular vesicles from adipose mesenchymal stem cells make important contributions to the pro-/antifibrotic balance. There is a growing evidence of important contribution of adipose tissue and its secretome to SSc pathogenesis. Novel techniques such as single-cell RNA sequencing (scRNAseq) and metabolomics, albeit challenging to use in adipose tissue, will provide further evidence.

The Use of Adipose-Derived Stem Cells (ADSCs) and Stromal Vascular Fraction (SVF) in Skin Scar Treatment-A Systematic Review of Clinical Studies.

In recent years, lipofilling became a popular scar treatment method. Its beneficial outcomes have been partly attributed to the regenerative capacity of adipose-derived stem cells (ADSCs), suspended in an extracellular matrix—the stromal vascular fraction (SVF). The aim of this review was to verify if existing data support the clinical use of ADSC-related interventions in scar treatment. A systematic search of the literature was performed in July 2020 in five databases (Medline, Cochrane, Web of Science, Scopus and Embase). Articles written in English, except for reviews, letters and editorials, were identified and screened for eligibility. We looked for reports of any outcomes in scars treated with ADSCs or SVF. Data from selected articles were extracted and the quality of each study was assessed. Five hundred and fourteen studies were identified in the primary search, of which nineteen were eventually included in the systematic review. Extracted data pointed to beneficial microscopic, functional and aesthetic outcomes in a total of 665 patients. Six studies included comparative interventions—platelet-rich plasma or CO2 fractional laser. Collected data give low-to-average quality evidence for beneficial effects of ADSC-related interventions in scar treatment. Some studies suggest that these interventions are noninferior to PRP or fractional CO2 laser.

In vitro evaluation of adipose-derived stromal vascular fraction combined with osteochondral integrated scaffold

In vitro evaluation of adipose-derived stromal vascular fraction combined with osteochondral integrated scaffold

The Effect of Adipose-Derived Stromal Vascular Fraction Cells to Abdominal Wall Fascia Defects in Rats: An Experimental Study

Objective Various synthetic and biological meshes have been developed to reduce recurrence and complications in ventral incisional hernia repairs. Adipose tissue is a rich reserve for mesenchymal stromal cells. In the present study we aimed to examine the effects of adipose-derived mesenchymal stromal cells (AD-MSCs) on abdominal incisional hernia repairs in rats. Materials and Methods The study involved 32 male Wistar-Albino rats, weighing 200–250 g, which were divided into three groups. In Group 1 (control group) only an incisional hernia model was created. In Group 2, the incisional hernia model was created and 1 ml stromal vascular fraction (SVF), obtained from inguinal lipectomy material and containing mesenchymal stromal cells, was injected into the edges of the defect in the same session. In Group 3, only the incisional hernia model was created in the first stage and after 14 days, 1 ml of SVF was injected into the edges of the defect. Skin incisions of rats in Group 1 and 2 were opened on postoperative day 28 while in group 3 were opened on day 42. Peritoneal formation in abdominal wall defect was evaluated macroscopically and histopathologically. Results Peritoneal formation was significantly superior in Groups 2 and 3 than in Group 1 (p: 0.031). In histopathological evaluation, the structural distortion and polymorphonuclear leukocyte (PMNL) levels were significantly higher in Group 1 than in Group 3 (p: 0.048 and p: 0.046, respectively). Granulation, capillary density, fibrosis and collagen organization were higher in Group 2 and 3, however this difference was not statistically significant (p > 0.05). Conclusions Adipose-derived stromal vascular fraction cells obtained from inguinal lipectomy material in rats positively affect the repair of abdominal incisional hernias by increasing peritoneal formation, and reducing structural distortion and PMNL infiltration.