Injection Of Stromal Vascular Fraction Research Articles

Cultured versus freshly isolated adipose-derived stem cells in improvement of the histopathological outcomes in HCL-induced cystitis in a rat model

Interstitial cystitis (IC) is an incurable chronic disease. The etiology of IC is unclear, and no effective therapies have been established. Here, using a hydrogen chloride (HCL)-induced IC in a rat model, the therapeutic potency of stromal vascular fraction (SVF) and Adipose-derived stem cells (ADSCs) was studied. Thirty-six female Sprague Dawley rats were divided into four groups: the sham, HCL, (HCL+SVF) group, and (HCL+ADSCs) group (9 for each). Cystitis was induced by transurethral instillation of HCL, while PBS was used for the sham group. A single dose of SVF or ADSCs was injected into the submucosa of the rat bladder in HCL-induced IC groups. The bladder tissues were analyzed for Toluidine Blue, Masson Trichrome, CD3, and CD34 to evaluate mast cell activation, fibrosis, inflammatory cells, and bladder regeneration, respectively. Compared to HCL-induced IC, SVF or ADSCs injection into IC bladder dramatically decreased mast cell infiltration, T-cell activation, and fibrosis. Taken together, administration of SVF cells or cultured ADSCs improves the histopathological outcomes of HCL-induced bladder injury in a time-dependent manner. Of note, SVF injection into the bladder submucosa was estimated to have the most potent therapeutic efficacy and may represent an essential component in future clinical applications.

Clinical Safety and Effectiveness of Adipose-Derived Stromal Cell vs Stromal Vascular Fraction Injection for Treatment of Knee Osteoarthritis: 2-Year Results of Parallel Single-Arm Trials

Background: There are currently no disease-modifying treatments available for knee osteoarthritis (OA), although cultured adipose-derived stromal cells (ASCs) have shown promise in experimental models. However, given the regulatory limits on the use of cultured cells in humans, previous trials have focused primarily on the stromal vascular fraction (SVF) intra-articular injection. Therefore, the therapeutic value of ASCs for knee OA remains unknown. Purpose: To study ASC versus SVF intra-articular injection in patients with Kellgren-Lawrence (KL) knee OA grades 2 to 4 in parallel single-arm trials. Study Design: Cohort study; Level of evidence, 2. Methods: A total of 80 patients were enrolled, with 42 (72 knees) receiving ASC intra-articular injection and 38 (69 knees) receiving SVF. Patient-reported outcome measures were assessed at 1, 3, 6, 12, and 24 months using the Knee injury and Osteoarthritis Outcome Score 5 (KOOS5) and pain visual analog scale (VAS). The percentages of patients achieving the minimal clinically important difference (MCID) and Patient Acceptable Symptom State (PASS) were also calculated. Per protocol, a subset of the ASC group received an ASC booster injection after 6 months. A repeated-measures analysis of variance compared results between treatment arms and by KL grade over time. Results: Patient-reported outcome measures improved substantially after both treatments (P < .05 at all time points), with the ASC group more likely to achieve the MCID (50% vs 24%; P = .01) and PASS (45% vs 24%; P = .04) for the pain VAS and the MCID (43% vs 16%; P = .02) for the KOOS5 at 12 months, although not at 24 months. Knees treated with ASC for KL grade 2/3 OA had significantly superior outcomes compared with those with KL grade 4 OA for the KOOS5 (P = .01) and pain VAS (P = .03), but no such difference was observed in knees treated with SVF. Three patients receiving ASCs (7%; all KL grade 3) sought additional nonoperative treatment by 24 months versus 9 patients receiving SVF (24%; all KL grade 3) (P = .06). ASC booster injections conferred no additional benefit. Notably, patients in the ASC cohort reported more injection-site pain and swelling after the booster injection than after the initial injection (P < .01). Conclusion: This represents the first head-to-head comparison of ASCs and SVF for the treatment of knee OA in humans. ASC and SVF injections both substantially improved knee pain and function at all follow-up time points, although ASC injections demonstrated significantly better improvements with regard to the MCID and PASS for the pain VAS and the MCID for the KOOS5 at 12 months. There appears to be no benefit to a booster ASC injection after initial treatment. Given less donor-site morbidity and equivalent superior outcomes at 2 years, the use of ASCs over SVF in the treatment of knee OA may be warranted.

Effect of Stromal Vascular Fraction on Sustained Volume Retention of Five Different Hyaluronic Acid Fillers.

The technology of manufacturing hyaluronic acid (HA) fillers is evolving to increase their safety and durability. This study aimed to compare the volume maintenance effect of stromal vascular fraction (SVF) on different types of HA fillers. In this controlled experiment, HA fillers mixed with SVF were injected into the right upper back and HA fillers alone were injected into the left upper back of each mouse. A total of 35 mice were separated into five groups according to the type of commercially used HA filler: Juvederm Voluma XC, Restylane Lyft, Restylane Skinboosters Vital, Giselle Ligne Signature 2, and Giselle Ligne Universal. Nodule size inspection was performed on post-injection days 0, 3, and 56. Ultrasonography for maximal two-dimensional area of filler nodule measurement and histology were performed on the last day of the inspection. While most of the groups showed a volume reduction of over 50% on day 56, regardless of SVF administration, significant volume maintenance was observed when Giselle Ligne Signature 2 was injected with SVF. Ultrasonographic measurement of two-dimensional filler nodule size showed no significant difference regarding filler types and SVF injection. When compared with the histological results of other fillers mixed with SVF, Giselle Ligne Signature 2 showed marked increase in cell survival and extracellular matrix components in HA particles. SVF showed different efficacies in terms of volume maintenance and cell survival for various HA filler types. The SVF mixture in selective HA filler injections may improve maintenance in clinical settings. This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Short-term results of intra-articular injections of stromal vascular fraction for early knee osteoarthritis

BackgroundIn knee osteoarthritis, progressive degeneration of the articular cartilage surface produces disability and chronic pain. Intra-articular injections of stromal vascular fraction (SVF) could be an innovative approach to manage patients with early knee osteoarthritis.MethodsBetween June 2019 and November 2020, 123 patients were recruited to receive intra-articular injection of SVF. Radiographic evidence of degenerative joint disease was classified according to Kellgren and Lawrence grades. Knee injury and osteoarthritis outcome score (KOOS) and visual analog scale (VAS) were collected preoperatively, at 1 month, and after 6 months from injection.ResultsThere was a statistically significant improvement of KOOS and VAS of all patients to 6 months (p < 0.05). The mean KOOS before injection was 51.4 ± 16.5, after 1 month it was 75.5 ± 15.8, and at 6 months it was 87.6 ± 7.7. Stratifying the mean KOOS according to Kellgren–Lawrence Grades, the difference remained statistically significant (p < 0.05). The patients’ mean VAS before injection was 6.5, after 1 month it was 3.5, and after 6 months it was 2.4. No complications were observed.ConclusionsIntra-articular knee injection of SVF is safe and effective to ameliorate the clinical and functional scores in patients with early knee osteoarthritis for 6 months.

Comparison of Stromal Vascular Fraction and Adipose-Derived Stem Cells for Protection of Renal Function in a Rodent Model of Ischemic Acute Kidney Injury.

Aims Few studies have compared the use of different cell types derived from adipose tissue or the optimal route for efficient and safe cell delivery in ischemic acute kidney injury (AKI). We compared the abilities of stromal vascular fraction (SVF) and adipose-derived stem cells (ADSC), injected via three different routes, to protect renal function in a rodent model of ischemic AKI. Methods Ninety male Sprague-Dawley rats were randomly divided into 9 groups: sham, nephrectomy control, AKI control, transaortic renal arterial SVF injection, renal parenchymal SVF injection, tail venous SVF injection, transaortic renal arterial ADSC injection, renal parenchymal ADSC injection, and tail venous ADSC injection groups. Their renal function was assessed 4 days before and 1, 2, 3, 4, 7, and 14 days after surgical procedures to induce ischemic AKI. The histomorphometric studies were performed 14 days after surgical procedures. Results Renal parenchymal injection of SVF notably reduced the level of serum blood urea nitrogen and creatinine elevation compared to the AKI control group. Renal parenchymal injection of SVF notably reduced the level of creatinine clearance decrease. In addition, collagen content was lower in the renal parenchymal SVF injection group, and fibrosis was reduced. Apoptosis was reduced in the renal parenchymal SVF injection group, and proliferation was increased. The expression levels of antioxidative markers such as glutathione reductase and peroxidase were higher in the renal parenchymal SVF injection group. Conclusions Our findings suggest that renal function is protected from ischemic AKI through renal parenchymal injection of SVF, which has enhanced antifibrotic, antiapoptotic, and antioxidative effects.

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

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 meta-analysis 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.

Adipose Stromal Vascular Fraction Reverses Mitochondrial Hyperfission in Coronary Microvessels in Aging

IntroductionIn aging post‐menopausal women, Coronary Microvascular Disease (CMD) leads to hyperconstricted tone, reduced perfusion and chronic micro‐ischemia with angina. We previously showed an age‐related increase in coronary microvascular ROS alongside increased prooxidant gene and protein expression associated with blunted vasodilation. Adipose Stromal Vascular Fraction (SVF) is a heterogenous cell population that reduces vascular ROS to improve vasodilation. Oxidative stress with aging may be mediated by mitochondrial dysfunction, including fission/fusion imbalance. Therefore, we hypothesize aging leads to mitochondrial hyperfission and reduced fusion gene and protein expression, reversed by SVF therapy.MethodsCoronary microvessels from young (YC, 4 months), old (OC, 24 months), or old + SVF (OSVF, tail vein injection 4 weeks prior to sacrifice) from female Fischer 344 rats were assessed via RNA sequencing (n=3) and immunofluorescence imaging of fission/fusion proteins Dynamin Related Protein 1 (DRP‐1) and Mitofusin 1 &amp; 2 (MFN1 &amp; 2). Morphometric analysis was accomplished using ImageJ and the MiNA Image‐J tool to analyze 60x confocal images of microvessels stained with antibodies against mitochondrial TOM20. Statistics were preformed using One‐Way ANOVA with Bonferroni post hoc analysis.ResultsGene expression of DRP‐1 was significantly reduced, and MFN‐1 significantly enhanced in OSVF vs. OC (p = 0.035, 0.019). There was no significant difference in gene expression of fission or fusion mediators Fis‐1, MFN‐2 or Opa‐1. Protein expression of DRP‐1 was enhanced with aging, reduced to youthful levels by SVF (p = 0.007, 0.033) (Fig.1a). There were no differences in MFN1 or MFN2 protein expression with aging, however, protein expression of MFN‐1 was significantly increased after SVF (YC vs. OSVF p = 0.003, OC vs. OSVF p &lt; .001). Mitochondrial aspect ratio and form factor were reduced in aging (p = 0.024, &lt; 0.001), restored to youthful levels by SVF (p = &lt; 0.001, &lt; 0.001) (Fig. 1b). Mitochondrial fission factor was elevated with aging (p = &lt; 0.001), reversed by SVF therapy (p = &lt; 0.001) (Fig. 1c). Mitochondrial area was reduced with aging (p = 0.002). Mitochondrial branch length and numbers of branches within a network were greatest in youth, significantly attenuated with aging (p &lt; 0.001, &lt; 0.001), and significantly increased (albeit not to youthful levels) with SVF therapy (OC vs. OSVF: p = 0.017, 0.011, YC vs. OSVF: p = 0.004, 0.003) (Fig. 1d).ConclusionsDuring youth, mitochondrial morphology is more rod‐like and interconnected, vs. punctate and isolated in aging. Injection of SVF reversed mitochondrial circularity and partially restored mitochondrial network density in aging. These findings were complimented by enhanced expression of DRP‐1 with aging with reduced DRP‐1 and enhanced MFN‐1 expression with SVF. SVF is a plausible therapy for CMD by reversing mitochondrial dysfunction including alleviating oxidative stress, attenuating mitochondrial fission, and rejuvenating mitochondrial fusion.

The Effect of Adipose Derived Stromal Vascular Fraction on Flap Viability in Experimental Diabetes Mellitus and Chronic Renal Disease

Background The presence of chronic renal disease(CRD) concurrently with diabetes mellitus(DM) increases the flap failure. Adipose derived stromal vascular fraction (SVF) is known to enhance skin flap viability in both healthy and diabetic individuals. The aim of this experimental study was to investigate the effect of SVF on skin flap viability in rats with DM and CRD. Methods 48 Sprague-Dawley rats were separated into four groups as follows: group I (control), group II (diabetes mellitus), group III (chronic renal disease), and group IV (diabetes with chronic renal disease).Two dorsal flaps were elevated. Flaps on left side of all groups received 0.5 cc of SVF, while same amount of plasma-buffered saline (PBS) was injected into right side. On postoperative day 7, flaps were harvested for macroscopic, histopathologic and biochemical assessments. Areas of flap survival were measured macroscopically. Blood level of vascular endothelial growth factor (VEGF) was measured after injection of SVF. Results Macroscopically, SVF has significantly improved flap viability (p < 0.05). Flap viability percentage was lower in DM and CRD groups when compared with healthy control group. In respect of new capillary formation, there was a statistically significant difference between SVF injected flaps and PBS injected sides (p < 0.05). Similarly, VEGF levels were higher in all study groups and there was a significant difference in comparison to control group (p < 0.05). Conclusions The study showed that injection of SVF increased flap viability via endothelial differentiation and neovascularization. In vivo function of stem cells might be impaired due to uremia and diabetes-related microenviromental changes.

Intraoperative Intradermal Application of Stromal Vascular Fraction into the Abdominal Suture Line: Histological Analysis of Abdominal Scar Tissue.

Stem cell therapy is a promising new approach to wound healing. Stromal vascular fraction is a heterogeneous collection of cells, including adipose-derived stem cells, which are traditionally isolated using a manual collagenase-based technique. To our knowledge, this is the first human study that histologically assesses the potential of intraoperative intradermal injection of stromal vascular fraction on skin regeneration. In this controlled study, 20 patients undergoing deep inferior epigastric perforator flap breast reconstruction and bilateral flank liposuction were included. Stromal vascular fraction was injected intradermally into one side of the abdominal suture line, while the other side served as a control. Outcome measures included analysis of stromal vascular fraction by flow cytometry, histological analysis of scar tissue, and scar photography. Cell yield for application and cell viability were 55.9 ± 28.5 × 106 and 75.1% ± 14.5%, respectively. Age and body mass index were positively correlated with the number of cells for application and adipose-derived stem cells. Mean vascular density, elastic fiber content, collagen maturity (scar index), epidermal thickness, and number of rete ridges all showed higher values on the treated side. Furthermore, the injected number of adipose-derived stem cells and pericytes positively correlated with vascular density. It is safe to speculate that intradermal stromal vascular fraction injection at the beginning of the healing process increases vascular density, collagen maturity and organization, elastic fiber content, epidermal thickness, epidermal-dermal anchoring of the scarring skin and is therefore responsible for improved skin regeneration. It is a viable and safe method that can be used as an adjunctive treatment in plastic surgery procedures where suboptimal wound healing is anticipated. 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 .

The Effect of Stromal Vascular Fraction on Scar Formation of Transverse Rectus Abdominis Muscle Flap Donor Sites: A Pilot Study

Background: Stromal vascular fraction (SVF), which plays a substantial role in wound healing, has been discussed in many recent studies concerning its positive effect on scar formation. Our study explored the effects of SVF on scar formation from partially-removed transverse rectus abdominis muscle (TRAM) flaps after inset.Methods: From December 2017 to May 2020, we enrolled 11 patients undergoing breast reconstruction performed by a single surgeon using the free TRAM flap. As a split-body, placebo-controlled study, SVF was subcutaneously injected into one side of the abdomen, and normal saline was injected into the other side of each patient. Scarring was evaluated using the Vancouver Scar Scale (VSS) and Patient Scar Assessment Questionnaire (PSAQ) at 1, 6, and 12 months after surgery, and histology was evaluated with immunofluorescence analysis at 6 months after surgery.Results: No statistically significant differences were noted in the total scores or subcategory score of the VSS and PSAQ between the test and control groups. Some patients showed more positive staining for alpha smooth muscle actin, collagen type I, and type III in the test group than in the control group. However, quantification of positively stained areas showed no statistically significant difference.Conclusion: Intraoperative SVF injection had no demonstrable clinical effect on scar quality. Histology with immunofluorescence analysis also failed to demonstrate any significant effect of SVF on scars at the microscopic level. Despite previous studies indicating the positive effects of SVF on scar quality, this pilot study questions its true effectiveness.

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.

Platelets and Adipose Stroma Combined for the Treatment of the Arthritic Knee

Knee osteoarthritis (OA) leads to significant pain and disability, prompting new cell-based injections to lessen the symptoms. Biological therapies such as autologous microfragmented adipose tissue (AMAT) and a stromal vascular fraction (SVF) are a common source for harvesting mesenchymal and progenitor cells. Platelet-rich plasma (PRP) is associated with cytokines and growth factors. Recent studies have reported good clinical outcomes with AMAT, SVF, and PRP in knee osteoarthritis treatment. However, the preparation, processing, and application technique are vital to achieving satisfactory results. Many studies have examined outcomes after AMAT, SVF, or PRP injection, with encouraging results. Still, there is a lack of studies describing a technique that combines both methods, the timing, and the amount of SVF or PRP injected. This technical note’s objective was to describe a standardized new technique composed of platelet and adipose stroma to treat knee osteoarthritis (OA) and the processing method.

Adipose micro-grafts enhance tendinopathy healing in ovine model: An in vivo experimental perspective study.

In Europe, approximatively 100 000 to 500 000 tendon repairs are performed every year. These procedures are associated with a considerable rate of postoperative complications (from 6% to 11%). Autologous micro‐grafts (AAMG) and stromal vascular fraction (SVF) have been shown to improve tendon healing in 60% to 70% of treated rodents. The purpose of this study was to evaluate the effects of AAMG in a sheep model with tendinopathy. We used sheep models because, as a large animal, they are more comparable to humans. The hypothesis was that SVF injection would improve tendon healing compared with the control group, reducing inflammatory and matrix degrading, while increasing anti‐inflammatory expression and collagen synthesis in the early stage of tendon injury. Sixteen Apennine sheep aged 2 to 5 years underwent 500 UI type I collagenase injection into both common calcaneal tendons (CCT) to induce tendinopathy. After 15 days (T0), one CCT in every ovine underwent randomly to 2.5 mL of AAMG obtained by mechanical disruption and the contralateral CCTs received no treatment. Clinical, ecographic, and sonographic evaluations were performed after 4 weeks (T1) and 8 weeks (T2). Histological, immunohistochemical, real‐time polymerase chain reaction (RT‐PCR), and biomechanical evaluations were performed at T2. At T2, the treated group showed a final tendon diameter (9.1 ± 1.4 mm) and a hardness expression (62%) that were similar to the original healthy tendon (8.1 ± 1.1 mm; 100%), with a significant recovery compared with the control group (9.5 ± 1.7 mm; 39%). Moreover, histological analysis of the treated group revealed an improvement in the fiber orientation score, fiber edema score, infiltrative‐inflammatory process, and necrosis score (4.3 ± 3.3) compared with control group (8.8 ± 2.9). Immunohistochemically, the treated group showed high expression of collagen 1, Factor VIII and significantly low expression of collagen 3. These data were confirmed by RT‐PCR analysis. The study findings suggested that AAMGs obtained through mechanical disruption present a safe, efficient, and reliable technique, enhancing tendon healing.

Clinical Efficacy of Bone Marrow Aspirate Concentrate Versus Stromal Vascular Fraction Injection in Patients With Knee Osteoarthritis: A Systematic Review and Meta-analysis

Background: Knee injection using either bone marrow aspirate concentrate (BMAC) or stromal vascular fraction (SVF) from adipose tissue has been shown to result in symptomatic improvement in patients with knee osteoarthritis (OA). It is still unclear whether one of these therapies is superior over the other. Purpose: To systematically report the clinical studies evaluating BMAC and SVF in the treatment of knee OA and to compare the clinical efficacy of these 2 injection therapies. Study Design: Meta-analysis; Level of evidence, 4. Methods: This meta-analysis was performed per the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines. Studies were included if they reported the clinical outcomes after a single BMAC or SVF injection in the knee joint of patients with OA. Studies evaluating preparations of culture-expanded stem cells were excluded. A random effects model was used; the clinical efficacy of BMAC or SVF injection was assessed using the standardized mean difference (SMD) and compared. Visual analog scale (VAS) scores for pain and Western Ontario and McMaster Universities Osteoarthritis (WOMAC) knee index were the primary outcomes. The level of statistical significance was set at P < .05. Results: Ten studies and 472 patients with knee OA who received either BMAC (233 patients) or SVF (239 patients) were included. Patients who received an injection had improved VAS outcomes (mean ± SD): from 5.8 ± 1.3 to 2.6 ± 17 for BMAC and from 6.4 ± 1.4 to 3.4 ± 0.5 for SVF. They also experienced significantly reduced pain (SMD [VAS], 2.6 for BMAC and 3.4 for SVF) and improved function (SMD [WOMAC], 1.4 for BMAC and 1.2 for SVF). However, the SVF injection had a significantly greater effect on pain reduction than did the BMAC injection (P < .0001). Based on WOMAC, the clinical effect of BMAC versus SVF knee injection in patients with knee OA was equivalent (P = .626). Results were limited by the presence of publication bias as well as variability in the preparation methods utilized in the BMAC and SVF injection protocols. Complications were reported in 50% of the BMAC studies (knee stiffness, persistent knee swelling) and 67% of the SVF studies (knee swelling, knee pain, positive SVF cultures without symptoms of infection, and bleeding at the abdominal harvest site). Conclusion: A single BMAC or SVF injection into the knee joint of patients with OA resulted in symptomatic improvement at short-term follow-up. However, SVF seemed to be more effective than did BMAC in the reduction of knee pain. There was significant variation in the BMAC and SVF injection preparation techniques used across the studies and a lack of stratification of outcomes based on the radiologic classification of OA. Therefore, these results should be taken with caution.

The stromal vascular fraction mitigates radiation-induced gastrointestinal syndrome in mice

BackgroundThe intestine is particularly sensitive to moderate-high radiation dose and the development of gastrointestinal syndrome (GIS) leads to the rapid loss of intestinal mucosal integrity, resulting in bacterial infiltration, sepsis that comprise patient survival. There is an urgent need for effective and rapid therapeutic countermeasures. The stromal vascular fraction (SVF) derived from adipose tissue is an easily accessible source of cells with angiogenic, anti-inflammatory and regenerative properties. We studied the therapeutic impact of SVF and its action on the intestinal stem cell compartment.MethodsMice exposed to the abdominal radiation (18 Gy) received a single intravenous injection of stromal vascular fraction (SVF) (2.5 × 106 cells), obtained by enzymatic digestion of inguinal fat tissue, on the day of irradiation. Mortality was evaluated as well as intestinal regeneration by histological analyses and absorption function.ResultsThe SVF treatment limited the weight loss of the mice and inhibited the intestinal permeability and mortality after abdominal irradiation. Histological analyses showed that SVF treatment stimulated the regeneration of the epithelium by promoting numerous enlarged hyperproliferative zones. SVF restored CD24+/lysozyme− and Paneth cell populations in the ISC compartment with the presence of Paneth Ki67+ cells. SVF has an anti-inflammatory effect by repressing pro-inflammatory cytokines, increasing M2 macrophages in the ileum and anti-inflammatory monocyte subtypes CD11b+Ly6clowCX3CR1high in the spleen.ConclusionsThrough the pleiotropic effects that contribute to limiting radiation-induced lethality, SVF opens up attractive prospects for the treatment of emergency GIS.

Combination of platelet rich plasma and stromal vascular fraction on the level of vascular endothelial growth factor in rat subjects experiencing deep dermal burn injury

BackgroundThe healing process of burns includes coagulation, inflammation, and remodeling. Vascular endothelial growth factor (VEGF) is involved throughout this healing process. Stem cells from the platelet-rich plasma (PRP) with stromal vascular fraction (SVF) can increase concentrations of growth factors, including VEGF. This is expected to accelerate burn healing. The aim of this study was to determine the effect of a combination of PRP and SVF on VEGF levels in a rats model of deep dermal burn wound healing. Materials and methodsThis is an experimental research study in rats using a post-test control group design with 4 groups: A) control, B) Vaseline, C) topical PRP and SVF, and D) PRP and SVF injection. Burn wounds were induced according to the modified Guo method. ResultsIn a rats model of deep dermal wound healing, topical Vaseline significantly increased serum VEGF compared to control. Topical application and injection of stem cells also significantly increased serum VEGF compared to control and Vaseline. The VEGF concentration was significantly higher following injection of PRP and SVF, suggesting that the injection route is more effective at increasing VEGF levels compared to the topical application of stem cells. ConclusionThe combination of PRP and SVF, either by injection or topical application, can increase VEGF levels during the healing process from deep dermal burns.

Use of Autologous Adipose-Derived Stromal Vascular Fractions in Revision Rhinoplasty for Severe Contractures in Asian Patients.

Autologous adipose-derived stromal vascular fraction treatments have been shown to elicit antiinflammatory, antifibrotic, immunomodulatory, angiogenic, and regenerative effects. Injections of adipose-derived stromal vascular fraction have been used to treat severely scarred tissues. Revision septorhinoplasty was performed in 40 patients with severely contracted noses. Clinical outcomes and adverse events were compared between one group of patients treated with adjuvant adipose-derived stromal vascular fraction injections and a control group of patients treated with adjuvant 0.9% preservative-free saline injections. In the adipose-derived stromal vascular fraction group, nasal lengths were estimated at 4.2 ± 0.2 cm at baseline to 5.1 ± 0.2 cm at 18 months after revision septorhinoplasty. The lengths of nasal tip projection improved from 2.2 ± 0.2 cm at baseline to 2.9 ± 0.1 cm 18 months after surgery. In addition, nasofrontal angles improved from 125.6 ± 5.1 degrees at baseline to 128.1 ± 4.8 degrees 18 months after surgery. Nasolabial angles in the adipose-derived stromal vascular fraction group were estimated at 105.8 ± 6.5 degrees at baseline and 94.9 ± 5.6 degrees 18 months after surgery. Of these, nasal length, nasal tip projection, and nasolabial angle, but not nasofrontal angle, values improved more in the adipose-derived stromal vascular fraction group than in the control group. Preoperative and postoperative adjuvant adipose-derived stromal vascular fraction treatment markedly improved the therapeutic outcomes of revision rhinoseptoplasty of severely contracted noses without major side effects. Therapeutic, III.

Assessment of safety and efficacy of intra-articular injection of stromal vascular fraction for the treatment of knee osteoarthritis-a systematic review.

Stromal vascular fraction (SVF) as an injectable regenerative therapy for knee osteoarthritis (OA) has gained recent popularity. However, there is no clear consensus on the outcomes of such treatment. We systematically reviewed available evidence on the use of SVF injection in the treatment of knee OA. The study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, with keyword search in PubMed, Scopus, and the Cochrane Library Database and related article search in Google Scholar. Clinical studies demonstrating effects of SVF in knee OA and published in English literature were included. Risk of bias assessment was done with modified Coleman Methodology Scoring (CMS). Eleven studies (9 prospective, 2 retrospective) that contributed to 290 knees in 200 patients were included. Two studies that contributed to 3718 knee injections were excluded from pooled analysis and were scrutinized separately. Majority of patients reported improvement in pain, range of motion (ROM), functional rating, six metre walking distance, and functional outcome scores. There was no major donor-site morbidity. There was only one reported case of knee joint infection and no case of tumour formation in relation to SVF injection. Intra-articular injection of SVF can be a simple, affordable, and minimally invasive treatment that could serve as an interim option for patients who failed other conservative and arthroscopic options. Intra-articular injection of SVF is a safe and effective technique for the management of knee OA. However, comparative Level I studies are needed to support the use of adjuvants with SVF and also to compare the use of SVF (with or without adjuvants) with ADMSCs, PRP, and bone marrow concentrate.

Adipose-derived stromal vascular fraction (SVF) cells for the treatment of non-reconstructable peripheral vascular disease in patients with critical limb ischemia: A 6-year follow-up showing durable effects.

We previously reported 18-month results post-injection of adipose-derived stromal vascular fraction (SVF) cells in 10 patients with end-stage peripheral vascular disease (PVD) in critical limb ischemia (CLI) and candidates for amputation, secondary to long-standing diabetes and/or arteriosclerotic disease. We documented positive clinical outcomes demonstrating pain relief as a change in the Rutherford score, improvement of ankle-brachial ratios (ABI), complete healing of 6 critical-size ulcers and evidence of neovascularization to the foot by MRI-based angiography. We now report persistency of the effect 6years post-procedure in five patients and 4years post-procedure in four additional patients who remained asymptomatic until death due to cardiac causes (patient 3) and lost from the study (patient 1). The 10th patient died early in the study. All treated extremities remain asymptomatic with increased ambulation, no recurrence of ulceration, and doppler color flow imaging at various vascular levels of the extremity demonstrating persistent blood flow and the presence of pulses doppler waveforms in the treated foot. Despite the extent of the disease, the contralateral extremities have not worsened significantly and no new ulcerations have appeared in any of the patients. Collectively, these data demonstrate that SVF injections have a durable long-term benefit forestalling further progression of the disease.

Clinical Efficacy and Safety of Injection of Stromal Vascular Fraction Derived from Autologous Adipose Tissues in Systemic Sclerosis Patients with Hand Disability: A Proof-Of-Concept Trial.

Background: Stromal vascular fraction (SVF) has recently emerged as a potential therapeutic modality, due to its multipotent cellular components in tissue regeneration. Systemic sclerosis (SSc) is a progressive autoimmune disease that results in hand disability by skin fibrosis and microangiopathies. We performed an open-label study to investigate the efficacy and safety of SVF injection in SSc patients (Clinical Trial number: NCT03060551). Methods: We gathered 20 SSc patients with hand disability, planning for a 24-week follow-up period. SVF was extracted from autologous adipose tissues, processed by the closed system kit, and injected into each finger of SSc patients. We observed various efficacy and safety profiles at each follow-up visit. Results: Among the 20 initially enrolled patients, eighteen received SVF injection, and were completely followed-up for the whole study period. Patients received 3.61 × 106 mesenchymal stem cells into each finger on average. Skin fibrosis, hand edema, and quality of life were significantly improved, and 31.6% of active ulcers were healed at 24 weeks after injections. Semiquantitative results of nailfold capillary microscopy were ameliorated. There was no single serious adverse event related to the procedure. Conclusions: Injection of SVF derived from autologous adipose tissues is tolerable, and shows clinical efficacy in SSc patients.