Adipose-derived Stromal Vascular Fraction Research Articles

In vitro Cytotoxicity Evaluation of Flowable Hyaluronic Acid-Acellular Stromal Vascular Fraction (HA-aSVF) Mixture for Tissue Engineering Applications.

The stromal vascular fraction (SVF) is an aqueous fraction isolated from the adipose tissue that constitutes different kinds of cells and extracellular matrix components. Hyaluronic acid (HA) is a linear polysaccharide in vertebrate tissues and is considered a potential tissue engineering scaffold due to its biocompatible nature. In this study, we have evaluated the cytotoxicity of xenofree HA in combination with an acellular component of adipose SVF (HA-aSVF) to propose it as a candidate biomaterial for future applications. 3-(4,5-dimethyl thiazolyl-2)-2,5-diphenyltetrazolium bromide assay of L-929 cells treated with HA-aSVF was used in our study. Data were normalized to cell control (untreated) and extracts of copper and ultra-high molecular weight polyethylene were used as positive (PC) and negative controls (NC). Fibroblast cells retained the morphology after 24 h of treatment with HA-aSVF mixture and exhibited a similar percentage of cell activity compared to NC. PC showed a positive cytotoxic response as expected. The cells incubated with HA-aSVF showed a linear increase in cell activity indicating proliferation. The mixture of HA and acellular SVF in its flowable form is non-cytotoxic and showed improved cell proliferation. Hence the mixture can be proposed as a biomaterial and can be further explored for specific tissue engineering applications.

346-OR: IL-10–Treated Adipose Stromal Vascular Fractions Reverse Insulin Resistance in a Type 2 Diabetes Mellitus Mouse Model

Low IL-10 production capacity is associated with type 2 diabetes. Targeting IL-10 in diabetes patients has resulted in inconsistent results. To test if IL-10-treated adipose stromal vascular fraction could be used to reverse diabetes-induced gluconeogenesis and insulin resistance, we purified stromal vascular fractions (SVFs) from adipose tissue from diabetic (Lepdb/db ) and nondiabetic (Lep+/+) mice, treated them with IL-10, and injected them into adipose tissue of diabetic mice. Injection of IL-10 into adipose tissue of diabetic mice decreased mRNA expression of IL-6 and IL-1β of adipose SVFs but did not change G6PC and PCK1 expression in liver. Injection of IL-10-treated SVFs into adipose tissue of diabetic mice significantly decreased CCL2 and IL-1β expression and increased IL-10 and Foxp3 expression of SVFs of Lepdb/db mice. Moreover, injection of IL-10-treated SVFs significantly increased IL-10 levels of adipose tissue and decreased G6PC and PCK1 and insulin resistance of liver in diabetic mice. Altogether, our data suggest that IL-10-treated adipose SVFs could be used to reverse diabetes-induced gluconeogenesis gene expression and insulin resistance in diabetes. These data suggest that modified-adipose stromal vascular fractions could be used as a promising cell therapy tool in alleviating insulin resistance in diabetes mellitus. Disclosure L. Chen: None. Funding National Science and Technology Council, Taiwan (110-2314-B-A49A-540-MY3)

Clinical use of autologous adipose-derived stromal vascular fraction cell injections for hip osteoarthritis

IntroductionCurrently, studies on adipose-derived stromal vascular fraction (SVF) cells are attracting increasing attention because they have the potential to differentiate into a subset of cell types, such as bone marrow-derived mesenchymal stromal cells (MSCs), and are easier to harvest than MSCs, thus making them easier to apply clinically. This study evaluated the short-term clinical outcomes of SVF cell therapy for hip osteoarthritis (OA). MethodsForty-two patients were enrolled in this study; these patients received a single injection comprising an average of 3.8 (standard deviation [SD], ±1.3) × 107 SVF cells into the hip joint. All patients were followed-up for at least 6 months. The mean age of the patients was 60.2 years (SD, ±9.4 years). Kellgren–Lawrence (KL) grades II, III, and IV based on radiography were 13, 13, and 16 patients, respectively. SVF cells were obtained from the subcutaneous fat of the abdomen or breech using a Celution® 800/CRS system. The average cell viability of SVF cells was 90.8% (SD, ±2.8%). Clinical assessments were performed using the Harris Hip Score (HHS), Japanese Orthopaedic Association Hip Disease Evaluation Questionnaire (JHEQ) score, and visual analog scale (VAS) score to evaluate pain. Images were evaluated using radiography, and T2 mapping values were obtained using a 1.5-T magnetic resonance imaging system. These clinical and imaging assessments were followed from preoperatively to 6 months postoperatively. ResultsThe HHS, JHEQ score, and VAS score improved significantly from 22.5 (SD, ±16.6), 26.6 (SD, ±11.3), and 75.5 (SD, ±15.8) preoperatively to 46.8 (SD, ±27.2), 39.4 (SD, ±19.7), and 46.5 (SD, ±27.9), respectively, at 6 months postoperatively. KL grade II showed significant improvement in clinical outcome from preoperative to postoperative, while KL grade IV showed slight or little improvement. The center edge angle, acetabular head index on the radiographs, and T2 mapping values did not change significantly from preoperatively to 6 months postoperatively. ConclusionsSVF cell injection in the hip joint showed good short-term clinical efficacy for reducing hip OA symptoms. SVF cell therapy is thus an innovative and effective treatment for hip OA.

Influence of Adipose-Derived Stromal Vascular Fraction on Resorption of a Large-Volume Free-Fat Transplant Evaluated Using T3D Optical Scanning

Background and Objectives: The main drawback of lipofilling is fat transplant volume loss, which makes long-term results unreliable. This study’s aim was to assess the influence of an adipose-derived stromal vascular fraction (SVF) on volume retention in large-volume fat grafts. Materials and Methods: A murine model was used for the in vivo evaluation of fat-graft volume changes over 6 months. We used 28 immunocompromised nude NU(NCr)-Foxn1nu mice and human fat tissue as a liposuction by-product. Part of the fat tissue was used for SVF preparation. We created a fat transplant without SVF (SVF-) and with SVF (SVF+) groups. Large-volume grafts were injected above the sacrum and scapula in the same animal. Volume loss was evaluated using three-dimensional optical scanning at 14 days (T1), 3 months (T2), and 6 months (T3) after transplantation. Scans were processed with Artec Studio software to obtain stereolithography files. The volumes were calculated in RapidForm software 2006. Results: The highest volume loss was observed above the scapula at T3 (SVF- 85%; SVF+ 75%). There was a significant difference in volume between SVF-/SVF+ for grafts above the sacrum at T2, with lower loss in SVF+, and the significance became stronger at T3. The difference in volume loss was also significant above the scapula between SVF-/SVF+ at T3. Conclusions: Although we found a beneficial effect of SVF on the long-term survival of large-volume fat tissue transplants, volume loss due to other contributing factors was high.

Extent of Tissue Washing Can Significantly Alter the Composition of Adipose-Derived Stromal Vascular Fraction Cell Preparations: Implications for Clinical Translation.

Stromal vascular fraction (SVF) cell preparations have recently attracted much interest as a form of autologous cell therapy. These heterogenous cell populations typically include some proportion of blood-derived cells (BDCs)-including both red blood cells (RBCs) and leukocytes (WBCs). The objectives of this paper were to evaluate the effects of tissue washing and hypotonic RBC lysis-separately and together-on BDC concentrations within SVF, and further to explore whether BDCs can confer detectable and modifiable effects on adipose-derived cell activity. Using various cell culture assays, flow cytometry and ELISA analysis of human-derived SVF preparations, we show that thorough washing of adipose tissue prior to enzymatic dissociation effectively removes RBCs from SVF preparations as well as standard lysis methods and significantly alters the type and relative quantities of WBCs. In addition, these studies demonstrate that potentially toxic RBC components are detectable for up to 1 week in cultures containing RBC lysate, but not those with intact RBCs, and, that culture-expanded cells proliferate significantly more in the presence of intact RBCs versus RBC lysis products or control media. Broadly, these data exemplify how different seemingly mundane tissue processing steps can significantly influence SVF identity/composition, purity, and potency. Based on the findings of this work, we propose that translational efforts in the field would benefit by a better understanding of the impact of RBCs, WBCs, and non-viable cells on the in vivo therapeutic activity of SVF therapies.

Adipose-Derived Stromal Vascular Fractions Are Comparable With Allogenic Human Umbilical Cord Blood–Derived Mesenchymal Stem Cells as a Supplementary Strategy of High Tibial Osteotomy for Varus Knee Osteoarthritis

To compare the clinical, radiologic, and second-look arthroscopic outcomes of high tibial osteotomy (HTO) with stromal vascular fraction (SVF) implantation versus human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSC) transplantation and identify the association between cartilage regeneration and HTO outcomes. Patients treated with HTO for varus knee osteoarthritis between March 2018 and September 2020 were retrospectively identified. In this retrospective study, among 183 patients treated with HTO for varus knee osteoarthritis between March 2018 and September 2020, patients treated with HTO with SVF implantation (SVF group; n= 25) were pair-matched based on sex, age, and lesion size with those who underwent HTO with hUCB-MSC transplantation (hUCB-MSC group; n= 25). Clinical outcomes were evaluated using the International Knee Documentation Committee score and Knee Injury and Osteoarthritis Outcome Score. Radiological outcomes evaluated were the femorotibial angle and posterior tibial slope. All patients were evaluated clinically and radiologically before surgery and during follow-up. The mean final follow-up periods were 27.8 ± 3.6 (range 24-36) in the SVF group and 28.2 ± 4.1 (range, 24-36) in the hUCB-MSC group (P= 0.690). At second-look arthroscopic surgery, cartilage regeneration was evaluated using the International Cartilage Repair Society (ICRS) grade. A total of 17 male and 33 female patients with a mean age of 56.2 years (range, 49-67 years) were included. At the time of second-look arthroscopic surgery (mean, 12.6 months; range, 11-15 months in the SVF group and 12.7 months; range, 11-14 months in the hUCB-MSC group, P= .625), the mean International Knee Documentation Committee score and Knee Injury and Osteoarthritis Outcome Score in each group significantly improved (P < .001 for all), and clinical outcomes at final follow-up further improved in both groups when compared with the values at second-look arthroscopic surgery (P < .05 for all). Overall ICRS grades, which significantly correlated with clinical outcomes, were similar between groups with no significant differences (P= .170 for femoral condyle and P= .442 for tibial plateau). Radiologic outcomes at final follow-up showed improved knee joint alignment relative to preoperative conditions but showed no significant correlation with clinical outcomes or ICRS grade in either group (P > .05 for all). Improved clinical and radiological outcomes and favorable cartilage regeneration were seen after surgery for varus Knee OA in both SVF and hUCB-MSC groups. Level III, retrospective comparative study.

Sexual dimorphism in obesity is governed by RELMα regulation of adipose macrophages and eosinophils.

Obesity incidence is increasing worldwide with the urgent need to identify new therapeutics. Sex differences in immune cell activation drive obesity-mediated pathologies where males are more susceptible to obesity comorbidities and exacerbated inflammation. Here, we demonstrate that the macrophage-secreted protein RELMα critically protects females against high-fat diet (HFD)-induced obesity. Compared to male mice, serum RELMα levels were higher in both control and HFD-fed females and correlated with frequency of adipose macrophages and eosinophils. RELMα-deficient females gained more weight and had proinflammatory macrophage accumulation and eosinophil loss in the adipose stromal vascular fraction (SVF), while RELMα treatment or eosinophil transfer rescued this phenotype. Single-cell RNA-sequencing of the adipose SVF was performed and identified sex and RELMα-dependent changes. Genes involved in oxygen sensing and iron homeostasis, including hemoglobin and lncRNA Gm47283/Gm21887, correlated with increased obesity, while eosinophil chemotaxis and response to amyloid-beta were protective. Monocyte-to-macrophage transition was also dysregulated in RELMα-deficient animals. Collectively, these studies implicate a RELMα-macrophage-eosinophil axis in sex-specific protection against obesity and uncover new therapeutic targets for obesity.

Mechanical and Enzymatic Digestion of Autologous Fat Grafting (A-FG): Fat Volume Maintenance and AD-SVFs Amount in Comparison.

Currently, several techniques for autologous fat graft (A-FG) preparation aimed at obtaining purified tissue exist. Both mechanical digestions via centrifugation, filtration, and enzymatic digestion were considered the most effective with different impacts in terms of adult adipose-derived stromal vascular fraction cells (AD-SVFs) amount that volume maintenance. This article aimed to report the in vivo and in vitro results, represented by fat volume maintenance and AD-SVFs amount, obtained by four different procedures of AD-SVFs isolation and A-FG purification based on centrifugation, filtration, centrifugation with filtration, and enzymatic digestion. A prospective, case-control study was conducted. In total, 80 patients affected by face and breast soft tissue defects were treated with A-FG and divided into four groups: n=20 were treated with A-FG enhanced with AD-SVFs obtained by enzymatic digestion (study group 1 [SG-1]); n=20 were treated with A-FG enhanced with AD-SVFs obtained by centrifugation with filtration (SG-2); n=20 were treated with A-FG enhanced with AD-SVFs obtained by only filtration (SG-3); n=20 were treated with A-FG obtained by only centrifugation according to the Coleman technique (control group [CG]). Twelve months after the last A-FG session, the volume maintenance percentage was analyzed by magnetic resonance imaging (MRI). Isolated AD-SVF populations were counted using a hemocytometer, and cell yield was reported as cell number/mL of fat. Starting with the same amount of fat analyzed (20mL), 50,000 ± 6956 AD-SVFs/mL were obtained in SG-1; 30,250 ± 5100 AD-SVFs/mL in SG-2; 33.333 ± 5650 AD-SVFs/mL in SG-3, while 500 AD-SVFs/mL were obtained in CG. In patients treated with A-FG enhanced with AD-SVFs obtained by automatic enzymatic digestion, a 63% ± 6.2% maintenance of fat volume restoring after 1year was observed compared with 52% ± 4.6% using centrifugation with filtration, 39% ± 4.4% using only centrifugation (Coleman), and 60% ± 5.0% using only filtration. In vitro AD-SVFs cell analysis indicated that filtration was the most efficient system-between mechanical digestion procedures-thanks to the highest amount of cells obtained with fewer cell structure damage, producing in vivo, the most volume maintenance after 1year. Enzymatic digestion produced the best number of AD-SVFs and the best fat volume maintenance. 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 http://www.springer.com/00266 .

Toward transplantation tolerance with adipose tissue-derived therapeutics.

Solid organ and composite tissue allotransplanation have been widely applied to treat end-stage organ failure and massive tissue defects, respectively. Currently there are a lot of research endeavors focusing on induction of transplantation tolerance, to relieve the burden derived from long-term immunosuppressant uptake. The mesenchymal stromal cells (MSCs) have been demonstrated with potent immunomodulatory capacities and applied as promising cellular therapeutics to promote allograft survival and induce tolerance. As a rich source of adult MSCs, adipose tissue provides additional advantages of easy accessibility and good safety profile. In recent years, the stromal vascular fraction (SVF) isolated from adipose tissues following enzymatic or mechanical processing without in vitro culture and expansion has demonstrated immunomodulatory and proangiogenic properties. Furthermore, the secretome of AD-MSCs has been utilized in transplantation field as a potential "cell-free" therapeutics. This article reviews recent studies that employ these adipose-derived therapeutics, including AD-MSCs, SVF, and secretome, in various aspects of organ and tissue allotransplantation. Most reports validate their efficacies in prolonging allograft survival. Specifically, the SVF and secretome have performed well for graft preservation and pretreatment, potentially through their proangiogenic and antioxidative capacities. In contrast, AD-MSCs were suitable for peri-transplantation immunosuppression. The proper combination of AD-MSCs, lymphodepletion and conventional immunosuppressants could consistently induce donor-specific tolerance to vascularized composite allotransplants (VCA). For each type of transplantation, optimizing the choice of therapeutics, timing, dose, and frequency of administration may be required. Future progress in the application of adipose-derived therapeutics to induce transplantation tolerance will be further benefited by continued research into their mechanisms of action and the development of standardized protocols for isolation methodologies, cell culture, and efficacy evaluation.

Spheroids derived from the stromal vascular fraction of adipose tissue self-organize in complex adipose organoids and secrete leptin

BackgroundAdipose tissue-derived stromal vascular fraction (SVF) harbors multipotent cells with potential therapeutic relevance. We developed a method to form adipose spheroids (AS) from the SVF with complex organoid structure and enhanced leptin secretion upon insulin stimulation.MethodsSVF was generated from the interscapular brown adipose tissue of newborn mice. Immunophenotype and stemness of cultured SVF were determined by flow cytometry and in vitro differentiation, respectively. Spheroids were generated in hanging drops and non-adherent plates and compared by morphometric methods. The adipogenic potential was compared between preadipocyte monolayers and spheroids. Extracellular leptin was quantified by immunoassay. Lipolysis was stimulated with isoprenaline and quantified by colorimetric methods. AS viability and ultrastructure were determined by confocal and transmission electron microscopy analyses.ResultsCultured SVF contained Sca1 + CD29 + CD44 + CD11b- CD45- CD90- cells with adipogenic and chondrogenic but no osteogenic potential. Culture on non-adherent plates yielded the highest quantity and biggest size of spheroids. Differentiation of AS for 15 days in a culture medium supplemented with insulin and rosiglitazone resulted in greater Pparg, Plin1, and Lep expression compared to differentiated adipocytes monolayers. AS were viable and maintained leptin secretion even in the absence of adipogenic stimulation. Glycerol release after isoprenaline stimulation was higher in AS compared to adipocytes in monolayers. AS were composed of outer layers of unilocular mature adipocytes and an inner structure composed of preadipocytes, immature adipocytes and an abundant loose extracellular matrix.ConclusionNewborn mice adipose SVF can be efficiently differentiated into leptin-secreting AS. Prolonged stimulation with insulin and rosiglitazone allows the formation of structurally complex adipose organoids able to respond to adrenergic lipolytic stimulation.

Adipose-derived stromal vascular fraction injection following core decompression and biochemistry artificial bone graft implantation in osteonecrosis of the femoral head.

To determine how adipose-derived stromal vascular fraction (SVF) injection following core decompression (CD) and biochemistry artificial bone graft implantation affects outcomes in patients with osteonecrosis of the femoral head (ONFH). A total of 19 patients (28 hips) with stage I-IIIA ONFH received adipose-derived SVF injection and combined core decompression and biochemistry artificial bone graft implantation, followed up for a minimum of two years. Disease progression was evaluated according to the Association Research Circulation Osseous (ARCO) staging system, and the change of the ratio of the necrotic volume to femoral head volume was calculated with MRI before and after operation. At the last follow-up, 15 hips remained stable, and 13 hips had a progression, according to the ARCO staging system. A total of eight hips (5 with ARCO stage II and 3 with staged IIIA at baseline) progressed to post-collapse stage (stage IIIB-IV). In total, seven of eight hips with post-collapse stage and one with IIIA stage at follow-up converted to THAs in an average of 17.5months (range, 11-68months) postoperatively. The mean ratio of the necrotic lesion volume to the femoral head significantly decreased in hips with ARCO stage I (17.9 ± 3.0% to 9.8 ± 1.3%, p = 0.012, Δ necrosis ratio = 8.1 ± 4.2%) and stage II (22.7 ± 6.3% to 17.1 ± 9.4%, p = 0.001, Δ necrosis ratio = 5.7 ± 6.6%) at baseline. For the eight hips that progressed to post-collapse stage, the mean necrosis ratio increased from 27.4 ± 5.4% to 31.1 ± 4.0% (p = 0.146), Δ necrosis ratio = - 3.7 ± 3.9%. For the other 20 hips radiological survived, the mean necrosis ratio improved from 19.9 ± 4.4% to 11.8 ± 3.3% (p < 0.001), with Δ necrosis ratio = 8.1 ± 4.9%. Adipose-derived SVF injection following core decompression and biochemistry artificial bone graft implantation is safe and could effectively repair the necrosis lesion and delay disease progression in patients with early-stage ONFH.

Anti-photoaging Effect of Micronized Fat in Ultraviolet B-Induced Human Dermal Fibroblasts.

Adipose-derived stromal vascular fraction and mesenchymal stem cells have been proven to reduce the effects of skin photoaging. However, there is no standardized protocol for their preparation. This study aimed to investigate the skin rejuvenation potential of micronized fat, obtained using a novel device attached with a trifoliate blade, in the ultraviolet B-induced human dermal fibroblasts model. Micronized fat was prepared to obtain adipose-derived stromal vascular fraction and the adipose-derived mesenchymal stem cells to stromal vascular fraction ratio was determined by flow cytometry. The ultraviolet B-induced human dermal fibroblasts model was constructed to identify the characteristic of the human dermal fibroblasts using Vamiten and S-100 immunostaining, observe their morphology, and measure the levels of photoaging related factors. After the previous steps were completed, different cell groups were co-cultured with ultraviolet B-induced human dermal fibroblasts and the extent of improvement of photoaging was evaluated. Micronized fat had a higher adipose-derived mesenchymal stem cells to stromal vascular fraction ratio than the control fat preparations. The ultraviolet B-induced human dermal fibroblasts model showed lowered levels of type I collagen and transforming growth factor-βand increased expression of matrix metalloproteinases, which are the characteristics of photoaging in normal human dermal fibroblasts. Compared to different cell groups co-cultured with ultraviolet B-induced human dermal fibroblasts, micronized fat could lower the expression of matrix metalloproteinases and increase the level of type I collagen but lower the level of transforming growth factor-β. Obtaining micronized fat is more effortless and clinically safer. Micronized fat has an anti-photoaging effect by inhibiting the expression of MMPs via MAPK signaling pathway.

CircINSR Inhibits Adipogenic Differentiation of Adipose-Derived Stromal Vascular Fractions through the miR-152/MEOX2 Axis in Sheep

Adipose tissue plays a crucial role in energy metabolism. Several studies have shown that circular RNA (circRNA) is involved in the regulation of fat development and lipid metabolism. However, little is known about their involvement in the adipogenic differentiation of ovine stromal vascular fractions (SVFs). Here, based on previous sequencing data and bioinformatics analysis, a novel circINSR was identified in sheep, which acts as a sponge to promote miR-152 in inhibiting the adipogenic differentiation of ovine SVFs. The interactions between circINSR and miR-152 were examined using bioinformatics, luciferase assays, and RNA immunoprecipitation. Of note, we found that circINSR was involved in adipogenic differentiation via the miR-152/mesenchyme homeobox 2 (MEOX2) pathway. MEOX2 inhibited adipogenic differentiation of ovine SVFs and miR-152 inhibited the expression of MEOX2. In other words, circINSR directly isolates miR-152 in the cytoplasm and inhibits its ability to promote adipogenic differentiation of ovine SVFs. In summary, this study revealed the role of circINSR in the adipogenic differentiation of ovine SVFs and its regulatory mechanisms, providing a reference for further interpretation of the development of ovine fat and its regulatory mechanisms.

Efficacy of Adipose-Derived Mesenchymal Stem Cells and Stromal Vascular Fraction Alone and Combined to Biomaterials in Tendinopathy or Tendon Injury: Systematic Review of Current Concepts

Background and Objectives: Tendon injury and tendinopathy are among the most frequent musculoskeletal diseases and represent a challenging issue for surgeons as well as a great socio-economic global burden. Despite the current treatments available, either surgical or conservative, the tendon healing process is often suboptimal and impaired. This is due to the inherent scarce ability of tendon tissue to repair and return itself to the original structure. Recently, Adipose-derived mesenchymal stem cells (ADSC) and stromal vascular fraction (SVF) have gained a central interest in the scientific community, demonstrating their effectiveness in treatments of acute and chronic tendon disorders in animals and humans. Either enzymatic or mechanical procedures to obtain ADSC and SVF have been described and used in current clinical practice. However, no unified protocols and processes have been established. Materials and Methods: This systematic review aims at providing a comprehensive update of the literature on the clinical application of ADSC enzymatically or mechanically processed to obtain SVF, alone and in association with biomaterials in the local treatment of tendinopathy and tendon injury in vivo, in animal models and humans. The study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Results: Thirty-two articles met our inclusion criteria, with a total of 18 studies in animals, 10 studies in humans and 4 studies concerning the application of biomaterials in vivo in animals. The review of the literature suggests that ADSC/SVF therapy can represent a promising alternative in tendonregenerative medicine for the enhancement of tendon healing. Conclusions: Nevertheless, further investigations and randomized control trials are needed to improve the knowledge, standardize the procedures and extend the consensus on their use for such applications.

The Therapeutic Application of Stem Cells and Their Derived Exosomes in the Treatment of Radiation-Induced Skin Injury.

Radiation-induced skin injury (RISI) is a serious concern for nuclear accidents and cancer radiotherapy, which seriously affects the quality of life of patients. This injury differs from traditional wounds due to impaired healing and the propensity to recurrence and is divided into acute and chronic phases on the basis of the injury time. Unfortunately, there are few effective therapies for preventing or mitigating this injury. Over the last few decades, various studies have focused on the effects of stem cell-based therapies to address the tissue repair and regeneration of irradiated skin. These stem cells modulate inflammation and instigate tissue repair by differentiating into specific kinds of cells or releasing paracrine factors. Stem cell-based therapies, including bone marrow-derived stem cells (BMSCs), adipose-derived stem cells (ADSCs) and stromal vascular fraction (SVF), have been reported to facilitate wound healing after radiation exposure. Moreover, stem cell-derived exosomes have recently been suggested as an effective and cell-free approach to support skin regeneration, circumventing the concerns respecting direct application of stem cells. Based on the literature on stem cell-based therapies for radiation-induced skin injury, we summarize the characteristics of different stem cells and describe their latest animal and clinical applications, as well as potential mechanisms. The promise of stem-cell based therapies against radiation-induced skin injury contribute to our response to nuclear events and smooth progress of cancer radiotherapy.

Effect of adipose derived stromal vascular fraction on leprosy neuropathy: A Preliminary report.

Adipose derived stromal vascular fraction (SVF) contains a heterogeneous population of mononuclear cells, progenitor cells and about 1-10% are mesenchymal stromal cells. These cells are an ideal candidate for regenerative medicine for peripheral neuropathy. Leprosy is a disabling disorder with neuropathy, usually with consequences of permanent disability of the extremities. We conducted a preliminary study to evaluate the cell yield, its characteristics and clinical outcomes after SVF injections in four leprosy patients. Four post leprosy patients were recruited and evaluated for sensory testing (warm detection, cold detection, vibration, pain and sensation) on the ulnar area of the hand. Liposuction was done and adipose tissue was processed into SVF with a closed system and injected to the ulnar area of the hand at the dorsal and palmar side. Evaluation of sensory testing was done after 3 days, 1 week, 1 month and 3 months following SVF injection. SVF was also characterized using flow cytometry, cell counting, sterility and presence of mycobacteria. The results showed that leprosy patients had a low count of mesenchymal cells and a high amount of CD34/CD45 positive cells. One patient was positive for mycobacteria from his adipose tissue and SVF. Sensory examination after SVF injection showed an improvement in temperature and pain sensation in the palmar and superficial branch. Meanwhile, touch sensation improved on the dorsal branch, and there was no improvement for vibration in all patients. The results showed that SVF had a potential to improve sensory loss in leprosy patients.

Clinical and Radiological Comparison of Single and Double Intra-articular Injection of Adipose-Derived Stromal Vascular Fraction for Knee Osteoarthritis

The aim of the article is to compare the clinical and radiological outcomes between single and double stromal vascular fraction (SVF) cell injections in patients with knee osteoarthritis (OA). We included 54 patients treated for varus knee OA with intra-articular SVF cell injection. They were divided into two groups: those who received one injection and those who received two. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, knee range of motion, and knee muscle force were assessed at baseline and 3, 6, 12, and 24 months after the first injection. The preoperative hip-knee-ankle (HKA) angle was evaluated using plain radiographs, and T2 mapping values were assessed. The total WOMAC score improved significantly in the single injection group from 3 to 24 months, but the total WOMAC score in the double injection group improved significantly at 24 months. The T2 mapping values in both the groups improved, with a significant difference at 12 months. The preoperative mean HKA angle and the correlation coefficients between the HKA angle and the total WOMAC score and between the HKA angle and the T2 mapping value of the medial femur were significant. In conclusion, double injections may provide more satisfactory treatment outcomes in patients with severe varus knee alignment. This clinical trial is registered in the Japanese Ministry of Health, Labour and Welfare (URL: https://saiseiiryo.mhlw.go.jp/published_plan/index/2) with the registration name “Cell transplantation therapy for osteoarthritis using autologous subcutaneous adipose tissue-derived regenerative (stem) cells (ADRCs),” and the registration number was “PB5160012.”

The Effect of Tissue Stromal Vascular Fraction as Compared to Cellular Stromal Vascular Fraction to Treat Anal Sphincter Incontinence.

The long-term prognosis of current treatments for anal sphincter incontinence (ASI) is poor. Here, we explored the efficacy of tissue adipose stromal vascular fraction SVF (tSVF) on ASI and compared it to that of cellular SVF (cSVF). We then investigated possible mechanisms. Rat cSVF and tSVF were isolated and labeled with DIL. One day after modeling, three groups received phosphate-buffered saline (PBS), cSVF, tSVF, respectively. The control group received nil modeling nor any treatments. The effect was assessed by function test for anal pressure and electromyography, and staining for fiber content, proliferation and differentiation at day 5 and day 10. cSVF injection resulted in faster healing than tSVF. The cSVF group showed significant improvement on anal pressure on day 10. For the electromyography test, cSVF showed significant improvement for the frequencies on day 10, and for the peak values on both time points, while tSVF showed significant improvement for the peak values on day 10. The two SVF both alleviated fibrosis. Immunofluorescence tracing identified differentiation of some injected cells towards myosatellite cells and smooth muscle cells in both SVF groups. For all the tests, the tSVF group tends to have similar or lower effects than the cSVF group with no significant difference. cSVF and tSVF are both safe and effective in treating ASI, while the effect of cSVF is slighter higher than tSVF.

Safety of Stromal Vascular Fraction Cell Therapy for Chronic Kidney Disease of Unknown Cause (Mesoamerican Nephropathy)

Chronic kidney disease of unknown cause (CKDu), also known as Mesoamerican nephropathy, typically presents as an ischemic nephropathy with chronic tubulointerstitial fibrosis in normotensive patients, rapidly progressing to kidney failure. In this first-in-human, open-label, safety study, we followed 18 patients with CKDu (stages 3-5) for 36 months after receiving a single infusion of angiogenic/anti-fibrotic autologous adipose-derived stromal vascular fraction (SVF) cells into their kidneys bilaterally via renal artery catheterization. SVF therapy was safe and well tolerated. There were no SVF-related serious adverse events and no procedural complications. Color Doppler evaluation at 2 months demonstrated increased perfusion to the interlobar and/or arcuate artery levels in each kidney evaluated (36/36) with a reduction in resistance index at the hilar artery (35/36) kidneys. Beyond 12 months, patients with initial eGFR <30 mL/minute/1.73 m2 deteriorated, whereas those ≥30 mL/minute/1.73 m2 further sustained their renal function, suggesting a possible renal protective effect in that group.

Emerging point-of-care autologous cellular therapy using adipose-derived stromal vascular fraction for neurodegenerative diseases.

Neurodegenerative disorders are characterized by the gradual decline and irreversible loss of cognitive functions and CNS structures. As therapeutic recourse stagnates, neurodegenerative diseases will cost over a trillion dollars by 2050. A dearth of preventive and regenerative measures to hinder regression and enhance recovery has forced patients to settle for traditional therapeutics designed to manage symptoms, leaving little hope for a cure. In the last decade, pre-clinical animal models and clinical investigations in humans have demonstrated the safety and promise of an emerging cellular product from subcutaneous fat. The adipose-derived stromal vascular fraction (SVF) is an early intervention and late-stage novel 'at point' of care cellular treatment, demonstrating improvements in clinical applications for Multiple Sclerosis, Alzheimer's disease, and Parkinson's disease. SVF is a heterogeneous fraction of cells forming a robust cellular ecosystem and serving as a novel and valuable source of point-of-care autologous cell therapy, providing an easy-to-access population that we hypothesize can mediate repair through 'bi-directional' communication in response to pathological cues. We provide the first comprehensive review of all pre-clinical and clinical findings available to date and highlight major challenges and future directions. There is a greater medical and economic urgency to innovate and develop novel cellular therapy solutions that enable the repair and regeneration of neuronal tissue that has undergone irreversible and permanent damage.