Tissue-derived Stromal Vascular Fraction Research Articles

Understanding and controlling the variables for stromal vascular fraction therapy.

In regenerative medicine, the isolation of mesenchymal stromal cells (MSCs) from the adipose tissue's stromal vascular fraction (SVF) is a critical area of study. Our review meticulously examines the isolation process of MSCs, starting with the extraction of adipose tissue. The choice of liposuction technique, anatomical site, and immediate processing are essential to maintain cell functionality. We delve into the intricacies of enzymatic digestion, emphasizing the fine-tuning of enzyme concentrations to maximize cell yield while preventing harm. The review then outlines the filtration and centrifugation techniques necessary for isolating a purified SVF, alongside cell viability assessments like flow cytometry, which are vital for confirming the efficacy of the isolated MSCs. We discuss the advantages and drawbacks of using autologous vs allogeneic SVF sources, touching upon immunocompatibility and logistical considerations, as well as the variability inherent in donor-derived cells. Anesthesia choices, the selection between hypodermic needles vs liposuction cannulas, and the role of adipose tissue lysers in achieving cellular dissociation are evaluated for their impact on SVF isolation. Centrifugation protocols are also analyzed for their part in ensuring the integrity of the SVF. The necessity for standardized MSC isolation protocols is highlighted, promoting reproducibility and successful clinical application. We encourage ongoing research to deepen the understanding of MSC biology and therapeutic action, aiming to further the field of regenerative medicine. The review concludes with a call for rigorous research, interdisciplinary collaboration, and strict adherence to ethical and regulatory standards to safeguard patient safety and optimize treatment outcomes with MSCs.

Cytokine production by bovine adipose tissue stromal vascular fraction cells upon Neospora caninum stimulation

In bovines few studies addressed the contribution of adipose tissue to the host immune response to infection. Here we evaluated the in vitro response of bovine adipose tissue stromal vascular fraction (SVF) cells to the protozoan parasite Neospora caninum, using live and freeze-killed tachyzoites. Live N. caninum induced the production of IL-6, IL-1β and IL-10 by SVF cells isolated from subcutaneous adipose tissue (SAT), while in mesenteric adipose tissue (MAT) SVF cell cultures only IL-1β and IL-10 production was increased, showing slight distinct responses between adipose tissue depots. Whereas a clear IL-8 increase was detected in peripheral blood leucocytes (PBL) culture supernatants in response to live N. caninum, no such increase was observed in SAT or MAT SVF cell cultures. Nevertheless, in response to LPS, increased IL-8 levels were detected in all cell cultures. IL-10 levels were always increased in response to stimulation (live, freeze-killed N. caninum and LPS). Overall, our results show that bovine adipose tissue SVF cells produce cytokines in response to N. caninum and can therefore be putative contributors to the host immune response against this parasite.

Effect of sternocleidomastoid flap repair and endoscopic injection of emulsified adipose tissue stromal vascular fraction in the treatment of refractory cervical anastomotic leak contaminating mediastinum.

Mediastinal infection caused by anastomotic leak is hard to cure, mainly because the poor drainage at the site of mediastinal infection leads to persistent cavity infection, which in turn becomes a refractory mediastinal abscess cavity after minimally invasive esophagectomy (MIE)-McKeown. Herein, we explored sternocleidomastoid (SCM) muscle flaps and emulsified adipose tissue stromal vascular fraction containing adipose-derived stem-cells to address this issue. We studied 10 patients with esophageal cancer who underwent MIE-McKeown + 2-field lymphadenectomy and developed anastomotic and mediastinal leak and received new technology treatment in the Affiliated Cancer Hospital of Zhengzhou University from June 2018 to March 2022. The clinical data and prognosis of the patients were collected and analyzed. A total of 5 patients received this surgery, and no other complications occurred during the perioperative period. Among the 5 patients, 1 patient was partially cured, and 4 patients were completely cured. During the follow-up 3 months postoperatively, all these 5 patients could eat regular food smoothly, and no relapse of leak and mediastinal infection occurred. The new surgical method has achieved good results in the treatment of anastomotic leak. Compared with the traditional thoracotomy, it is a less invasive and feasible surgical approach, which can be used as a supplement to the effective surgical treatment of cervical anastomotic leak contaminating the mediastinum.

Effect of adipose tissue-derived stromal vascular fraction on the viability of random-pattern skin flaps: an experimental study

Aims: Random pattern skin flaps are still widely used in plastic surgery. However, necrosis in distal flap sections resulting from ischemia is a serious problem, increasing the cost of treatment and hospitalization. The aim of this study was to test the effects of adipose tissue derived stromal vascular fraction (SVF) on random pattern skin flaps in rats. Methods: In this experimental study conducted on Wistar rats, three groups were formed using the simple random sampling technique. Group 1 consisted of rats with a raised flap and a subcutaneous SVF injection. Group 2 comprised rats that underwent a flap operation with no additional treatment. Group 3 included rats with a raised flap and a subcutaneous saline injection. Tissue necrosis and level of survival area was detected with planimetric method and histopathologic examination was performed for detect of level of vascular density. On the 7th day post-operation, the viability assessment was calculated based on the ratio of the living flap area to the total flap area. Results: The mean viability rate in Group 1 was higher compared to other groups, while there was no significant difference between Group 2 and Group 3 (Group 1 = 79.2 ± 4.9 % vs. Group 2 = 41.0 ± 5.9 % vs. Group 3= 39.2 ± 2.7 %, p < 0.001). The mean vascular densities of the flaps were higher in Group 1 compared to the other groups, while it were similar between Group 2 and Group 3 (Group 1 = 29.8 ± 1.2 vs. Group 2 = 8.4 ± 4.6 vs. Group 3= 9.3 ± 1.8, p < 0.001). Conclusion: The use of fat tissue-derived SVF injections has been found to be advantageous in improving the survival of random pattern flaps, frequently utilized in plastic and reconstructive surgery.

LncRNA U90926 is dispensable for the development of obesity-associated phenotypes invivo.

Obesity is a global health problem characterized by excessive fat accumulation, driven by adipogenesis and lipid accumulation. Long non-coding RNAs (lncRNAs) have recently been implicated in regulating adipogenesis and adipose tissue function. Mouse lncRNA U90926 was previously identified as a repressor of invitro adipogenesis in 3T3-L1 preadipocytes. Consequently, we hypothesized that, invivo, U90926 may repress adipogenesis, and hence its deletion would increase weight gain and adiposity. We tested the hypothesis by applying U90926-deficient (U9-KO) mice to a high-throughput phenotyping pipeline. Compared with WT, U9-KO mice showed no major differences across a wide range of behavioral, neurological, and other physiological parameters. In mice fed a standard diet, we have found no differences in obesity-related phenotypes, including weight gain, fat mass, and plasma concentrations of glucose, insulin, triglycerides, and free fatty acids, in U9-KO mice compared to WT. U90926 deficiency lacked a major effect on white adipose tissue morphology and gene expression profile. Furthermore, in mice fed a high-fat diet, we found increased expression of U90926 in adipose tissue stromal vascular cell fraction, yet observed no effect of U90926 deficiency on weight gain, fat mass, adipogenesis marker expression, and immune cell infiltration into the adipose tissue. These data suggest that the U90926 lacks an essential role in obesity-related phenotypes and adipose tissue biology invivo.

Bone defect management with tissue-engineered constructs based on deproteinized cancellous bone: an experimental study

Background Management of bone defects with autologous bone grafting has always been the "gold standard" but it is not always possible to use it for a number of reasons. Preprocessed materials of biological and non-biological origin were developed as an alternative. A new branch of these materials is tissue-engineered constructs that fully imitate autologous bone in required volume.Aim is to study in vivo the possibility of using deproteinized human cancellous bone tissue as a matrix for creating tissue-engineered constructs.Methods The study was carried out on 24 NZW line rabbits, since this line has a fully characterized stromal-vascular fraction formula (SVF). The study design included 3 groups. First group (control) had surgical modeling of bone defects in the diaphysis of the contralateral femur without reconstruction; Group 2 had bone defect reconstruction using fragments of a deproteinized cancellous bone graft; group 3 underwent bone defect reconstruction using fragments of deproteinized cancellous bone matrix along with the autologous adipose tissue SVF (obtained according to ACP SVF technology). Animals were sacrificed with ether anesthesia at 2, 4 and 6 weeks after the operation and subsequent histological study followed.Result During all periods of the study, the newly formed bone tissue volume density in the 3rd group (reconstruction with deproteinized human cancellous bone + stromal-vascular fraction) was 1.78 times higher (p < 0.001) than in the first group (bone defect without reconstruction), 1.21 times higher (p < 0.001) than in the 2nd group (reconstruction with deproteinized cancellous bone alone). The dynamics of changes in the mature bone tissue volume density was similar to those of the newly formed bone tissue.Discussion The comparative analysis of reparative processes using a tissue engeneered construst based on deproteinized cancellous human bone with adipose tissue stromal vascular fraction revealed that the use of these bone substitute materials contributes not only to the early activation of reparative regeneration of the main structural elements of bone tissue at the site of bone defect, but also their timely differentiation.Conclusion The use of deproteinized cancellous bone matrix combined with stromal-vascular fraction to create a tissue-engineered construct could unleash several regeneration mechanisms and accelerate the process of bone defect site repair, compared with 1st and 2nd group of study.

Mechanical Fractionation of Adipose Tissue-A Scoping Review of Procedures to Obtain Stromal Vascular Fraction.

Clinical indications for adipose tissue therapy are expanding towards a regenerative-based approach. Adipose-derived stromal vascular fraction consists of extracellular matrix and all nonadipocyte cells such as connective tissue cells including fibroblasts, adipose-derived stromal cells (ASCs) and vascular cells. Tissue stromal vascular fraction (tSVF) is obtained by mechanical fractionation, forcing adipose tissue through a device with one or more small hole(s) or cutting blades between syringes. The aim of this scoping review was to assess the efficacy of mechanical fractionation procedures to obtain tSVF. In addition, we provide an overview of the clinical, that is, therapeutic, efficacy of tSVF isolated by mechanical fraction on skin rejuvenation, wound healing and osteoarthritis. Procedures to obtain tissue stromal vascular fraction using mechanical fractionation and their associated validation data were included for comparison. For clinical outcome comparison, both animal and human studies that reported results after tSVF injection were included. We categorized mechanical fractionation procedures into filtration (n = 4), centrifugation (n = 8), both filtration and centrifugation (n = 3) and other methods (n = 3). In total, 1465 patients and 410 animals were described in the included clinical studies. tSVF seems to have a more positive clinical outcome in diseases with a high proinflammatory character such as osteoarthritis or (disturbed) wound healing, in comparison with skin rejuvenation of aging skin. Isolation of tSVF is obtained by disruption of adipocytes and therefore volume is reduced. Procedures consisting of centrifugation prior to mechanical fractionation seem to be most effective in volume reduction and thus isolation of tSVF. tSVF injection seems to be especially beneficial in clinical applications such as osteoarthritis or wound healing. Clinical application of tSVF appeared to be independent of the preparation procedure, which indicates that current methods are highly versatile.

Inhibition of nucleotide biosynthesis disrupts lipid accumulation and adipogenesis

Energy balance and nutrient availability are key determinants of cellular decisions to remain quiescent, proliferate, or differentiate into a mature cell. After assessing its environmental state, the cell must rewire its metabolism to support distinct cellular outcomes. Mechanistically, how metabolites regulate cell fate decisions is poorly understood. We used adipogenesis as our model system to ascertain the role of metabolism in differentiation. We isolated adipose tissue stromal vascular fraction cells and profiled metabolites before and after adipogenic differentiation to identify metabolic signatures associated with these distinct cellular states. We found that differentiation alters nucleotide accumulation. Furthermore, inhibition of nucleotide biosynthesis prevented lipid storage within adipocytes and downregulated the expression of lipogenic factors. In contrast to proliferating cells, in which mechanistic target of rapamycin complex 1 is activated by purine accumulation, mechanistic target of rapamycin complex 1 signaling was unaffected by purine levels in differentiating adipocytes. Rather, our data indicated that purines regulate transcriptional activators of adipogenesis, peroxisome proliferator-activated receptor γ and CCAAT/enhancer-binding protein α, to promote differentiation. Although de novo nucleotide biosynthesis has mainly been studied in proliferation, our study points to its requirement in adipocyte differentiation.

Adipose Tissue-Derived Components: From Cells to Tissue Glue to Treat Dermal Damage.

In recent decades, adipose tissue transplantation has become an essential treatment modality for tissue (volume) restoration and regeneration. The regenerative application of adipose tissue has only recently proven its usefulness; for example, the method is useful in reducing dermal scarring and accelerating skin-wound healing. The therapeutic effect is ascribed to the tissue stromal vascular fraction (tSVF) in adipose tissue. This consists of stromal cells, the trophic factors they secrete and the extracellular matrix (ECM), which have immune-modulating, pro-angiogenic and anti-fibrotic properties. This concise review focused on dermal regeneration using the following adipose-tissue components: adipose-tissue-derived stromal cells (ASCs), their secreted trophic factors (ASCs secretome), and the ECM. The opportunities of using a therapeutically functional scaffold, composed of a decellularized ECM hydrogel loaded with trophic factors of ASCs, to enhance wound healing are explored as well. An ECM-based hydrogel loaded with trophic factors combines all regenerative components of adipose tissue, while averting the possible disadvantages of the therapeutic use of adipose tissue, e.g., the necessity of liposuction procedures with a (small) risk of complications, the impossibility of interpatient use, and the limited storage options.

Tissue buccal fat pad–stromal vascular fraction as a safe source in maxillofacial bone regeneration: A clinical pilot study

The purpose of this study was to examine the biological properties of the buccal fat pad (BFP)-derived tissue stromal vascular fraction (tSVF) in vitro and compare them with BFP-derived cellular SVF (cSVF). Furthermore, a clinical pilot study assessed the safety of using BFP-derived tSVF for maxillofacial bone regeneration. This study was performed in two sections: 1) experimental section: BFP tissue was harvested from three healthy donors, and then cSVF and tSVF were isolated by enzymatic and mechanical methods to assess their biological properties and 2) clinical section: Ten patients with maxillofacial bone defects were enrolled according to eligibility criteria and offered two options for surgery, including autologous BFP-tSVF (n=5) and autologous bone grafting (n=5), to evaluate safety after a year of follow-up. The BFP-tSVF exhibited high cell viability and various cell surface markers, including CD45, CD31, and CD34. There was no population-doubling time and multilineage differentiation capacity compared with BFP-cSVF. BFP-tSVF is safe because of the lack of intervention-related adverse events reported in donor and surgery sites during a one-year period. In addition, cell therapy was feasible because it can be performed during surgery and requires little preparation time.Patients in the ABG group experienced pain and tenderness in the iliac crest, leading to dissatisfaction and complications. The experimental results confirmed that the cells isolated from BFP-tSVF have stemness properties similar to BFP-cSVF. Clinical evaluation also indicated that this cellular product could be used safely to regenerate maxillofacial bone defects.

Лечение остеоартроза коленных суставов на основе применения клеточных технологий

Osteoarthritis (OA) is the most common chronic disease of joint and a major cause of joint pain and disability. Traditional therapies for knee osteoarthritis show little clinical benefit, and the terminal treatment option is joint replacement. Currently, cell therapy is prospective for the treatment of knee osteoarthritis and has shown significant results in animal studies and human clinical trials. The aim: to investigate the treatment results in patients with knee osteoarthritis using adipose tissue stromal-vascular fraction and synovial mesenchymal stem cells.Methods. 60 patients with knee osteoarthritis were included in the study. The stage of knee osteoarthritis was assessed using the Kellgren-Lawrence classification, and patients with stage II-III of osteoarthritis were included in this study. After arthroscopic debridement, patients were divided into 2 groups. The first group was injected with the stromal-vascular fraction (SVF) of synovial membrane, and the second group was injected with adipose tissue mesenchymal stem cells (SVF). The minimum clinical and radiologic follow-up period was 12 months. Results. The assessment of the joints condition after 12 months using different scales showed that in both experimental groups there was a significant improvement of the functional status of the knee of the patients after treatment with MSC and SVF. Functional indicators of knee joints on the WOMAC scale improved by 14.7 and 13.4, on the KOOS scale by 23.6 and 26.4 in the SVF and MSC groups, respectively. Pain syndrome regressed by 1.8 and 2.1 on the VAS scale in the SVF and MSC groups, respectively.Conclusion. The results of both study groups showed that there is a significant difference between WOMAC, VAS and KOOS values before and after surgery (8, 12 weeks and 12 months) in the compared groups towards improvement

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.

Factors Affecting the Population of Mesenchymal Stem Cells in Adipose-Derived Stromal Vascular Fraction

Recently, the adipose tissue-derived stromal vascular fraction has become the most popular source for obtaining mesenchymal stem cells because it is less expensive and is easier to perform than bone marrow concentrate harvesting. However, no study has investigated the factors affecting the mesenchymal stem cell population in adipose tissue derived stromal vascular fraction. Understanding the interaction of patient factors with the mesenchymal stem cell count and cell viability in adipose tissue-derived stromal vascular fraction could provide crucial information for surgeons to improve patient selection and outcomes. To evaluate the factors affecting the mesenchymal stem cell count, total cell count, and cell viability in adipose tissue-derived stromal vascular fraction. Retrospective cross-sectional study. This study retrospectively reviewed the medical records of 30 patients who underwent liposuction to harvest adipose tissue-derived stromal vascular fraction at our stem cell center. Operative variables, such as lipoaspirate amount and donor areas from the stromal vascular fraction harvesting site, included the entire abdomen and lower abdomen. We recorded the mesenchymal stem cell population, cell viability, and cell count of stromal vascular fraction, and we analyzed the results to determine statistical significance. The factors that were found to be significantly related are as follows; between cell number and age (p=0.001) and amount of lipoaspirate (p<0.001); between cell viability and body mass index (p=0.005) and hypertension (p=0.047); and between coronary artery disease and mesenchymal stem cell counts (p = 0.028). The relationship of patient factors (age, body mass index, hypertension, and coronary artery disease) with cell viability and mesenchymal stem cell counts may be important for clinical applications. However, the effect of medications on these relationships should be investigated in larger studies.

Autologous Adipose-Derived Tissue Stromal Vascular Fraction (AD-tSVF) for Knee Osteoarthritis.

Adipose tissue contains adult mesenchymal stem cells that may modulate the metabolism when applied to other tissues. Stromal vascular fraction (SVF) can be isolated from adipose tissue mechanically and/or enzymatically. SVF was recently used to decrease the pain and improve the function of knee osteoarthritis (OA) patients. Primary and/or secondary OA causes inflammation and degeneration in joints, and regenerative approaches that may modify the natural course of the disease are limited. SVF may modulate inflammation and initiate regeneration in joint tissues by initiating a paracrine effect. Chemokines released from SVF may slow down degeneration and stimulate regeneration in joints. In this review, we overviewed articular joint cartilage structures and functions, OA, and macro-, micro-, and nano-fat isolation techniques. Mechanic and enzymatic SVF processing techniques were summarized. Clinical outcomes of adipose tissue derived tissue SVF (AD-tSVF) were evaluated. Medical devices that can mechanically isolate AD-tSVF were listed, and publications referring to such devices were summarized. Recent review manuscripts were also systematically evaluated and included. Transferring adipose tissues and cells has its roots in plastic, reconstructive, and aesthetic surgery. Micro- and nano-fat is also transferred to other organs and tissues to stimulate regeneration as it contains regenerative cells. Minimal manipulation of the adipose tissue is recently preferred to isolate the regenerative cells without disrupting them from their natural environment. The number of patients in the follow-up studies are recently increasing. The duration of follow up is also increasing with favorable outcomes from the short- to mid-term. There are however variations for mean age and the severity of knee OA patients between studies. Positive outcomes are related to the higher number of cells in the AD-tSVF. Repetition of injections and concomitant treatments such as combining the AD-tSVF with platelet rich plasma or hyaluronan are not solidified. Good results were obtained when combined with arthroscopic debridement and micro- or nano-fracture techniques for small-sized cartilage defects. The optimum pressure applied to the tissues and cells during filtration and purification of the AD-tSVF is not specified yet. Quantitative monitoring of articular joint cartilage regeneration by ultrasound, MR, and synovial fluid analysis as well as with second-look arthroscopy could improve our current knowledge on AD-tSVF treatment in knee OA. AD-tSVF isolation techniques and technologies have the potential to improve knee OA treatment. The duration of centrifugation, filtration, washing, and purification should however be standardized. Using gravity-only for isolation and filtration could be a reasonable approach to avoid possible complications of other methodologies.

Mechanically Derived Tissue Stromal Vascular Fraction Acts Anti-inflammatory on TNF Alpha-Stimulated Chondrocytes In Vitro.

Enzymatically isolated stromal vascular fraction (SVF) has already shown to be effective as a treatment for osteoarthritis (OA). Yet, the use of enzymes for clinical purpose is highly regulated in many countries. Mechanical preparation of SVF results in a tissue-like SVF (tSVF) containing intact cell–cell connections including extracellular matrix (ECM) and is therefore less regulated. The purpose of this study was to investigate the immunomodulatory and pro-regenerative effect of tSVF on TNFα-stimulated chondrocytes in vitro. tSVF was mechanically derived using the Fractionation of Adipose Tissue (FAT) procedure. Characterization of tSVF was performed, e.g., cellular composition based on CD marker expression, colony forming unit and differentiation capacity after enzymatic dissociation (from heron referred to as tSVF-derived cells). Different co-cultures of tSVF-derived cells and TNFα-stimulated chondrocytes were analysed based on the production of sulphated glycosaminoglycans and the anti-inflammatory response of chondrocytes. Characterization of tSVF-derived cells mainly contained ASCs, endothelial cells, leukocytes and supra-adventitial cells. tSVF-derived cells were able to form colonies and differentiate into multiple cell lineages. Co-cultures with chondrocytes resulted in a shift of the ratio between tSVF cells: chondrocytes, in favor of chondrocytes alone (p < 0.05), and IL-1β and COX2 gene expression was upregulated in TNFα-treated chondrocytes. After treatment with (a conditioned medium of) tSVF-derived cells, IL-1β and COX2 gene expression was significantly reduced (p < 0.01). These results suggest mechanically derived tSVF stimulates chondrocyte proliferation while preserving the function of chondrocytes. Moreover, tSVF suppresses TNFα-stimulated chondrocyte inflammation in vitro. This pro-regenerative and anti-inflammatory effect shows the potential of tSVF as a treatment for osteoarthritis.

Response to: Thoughts on Tissue Stromal Vascular Fraction for Early Scar Healing.

Response to: Thoughts on Tissue Stromal Vascular Fraction for Early Scar Healing.

Characterization and functional analysis of the adipose tissue-derived stromal vascular fraction of pediatric patients with osteogenesis imperfecta

Pediatric patients with Osteogenesis Imperfecta (OI), a heritable connective tissue disorder, frequently suffer from long bone deformations. Surgical correction often results in bone non-unions, necessitating revision surgery with autogenous bone grafting using bone-marrow-derived stem cells (BM-SC) to regenerate bone. BM-SC harvest is generally invasive and limited in supply; thus, adipose tissue's stromal vascular fraction (SVF) has been introduced as an alternative stem cell reservoir. To elucidate if OI patients' surgical site dissected adipose tissue could be used as autologous bone graft in future, we investigated whether the underlying genetic condition alters SVF's cell populations and in vitro differentiation capacity. After optimizing SVF isolation, we demonstrate successful isolation of SVF of pediatric OI patients and non-OI controls. The number of viable cells was comparable between OI and controls, with about 450,000 per gram tissue. Age, sex, type of OI, disease-causing collagen mutation, or anatomical site of harvest did not affect cell outcome. Further, SVF-containing cell populations were similar between OI and controls, and all isolated SVF's demonstrated chondrogenic, adipogenic, and osteogenic differentiation capacity in vitro. These results indicate that SVF from pediatric OI patients could be used as a source of stem cells for autologous stem cell therapy in OI.

Survivin is essential for thermogenic program and metabolic homeostasis in mice

ObjectiveSurvivin is a member of the inhibitor of apoptosis family. Our previous study showed that survivin expression could be strongly induced by long-term, high-fat diet (HFD) exposure in vivo. It could also be induced by insulin through the PI3K/mTOR signaling pathway in vitro. Therefore, we hypothesized that under certain conditions, survivin expression might be required for adipocyte function. In the current study, we aim to further investigate the regulation of survivin expression in mature adipocytes upon various nutritional stimuli and the role of survivin using adipocyte-specific survivin knockout (SKO) mice. MethodsSKO mice were obtained by crossing survivinflox/flox mice with Adiponectin-Cre+/- mice. The overall metabolic phenotype was observed under chow diet (CD) and HFD feeding conditions. The thermogenic program of mice was detected upon cold exposure. The inguinal white adipose tissue (iWAT) and brown adipose tissue (BAT) stromal vascular fraction cells were isolated and differentiated into mature adipocytes, and the effects of survivin deletion on mature adipocyte function were detected in vitro. ResultsSurvivin expression in adipose tissue and adipocytes was regulated by short-term nutritional stress both in vivo and in vitro. The postnatal development of BAT was impaired in SKO mice, which resulted in drastically reduced BAT mass and decreased expression of the thermogenic protein Ucp1 in 24-week-old mice fed with CD. After HFD feeding, the iWAT and BAT mass of SKO mice were significantly decreased, causing ectopic lipid accumulation in the liver, which was associated with insulin resistance and glucose intolerance. Upon cold exposure, the expression of thermogenic genes and proteins was markedly reduced in BAT and iWAT of SKO mice, accompanied by abnormal mitochondrial structure and induced autophagy. Consistently, thermogenic program and mitochondrial oxidative phosphorylation were reduced in survivin-depleted brown and beige adipocytes in vitro. ConclusionsOur findings showed that survivin could be regulated by nutritional stress in adipocytes and revealed a new role of survivin in maintaining normal BAT mass and positively regulating the thermogenic program and mitochondrial oxidative phosphorylation.

Tissue Stromal Vascular Fraction Improves Early Scar Healing: A Prospective Randomized Multicenter Clinical Trial.

Wound healing and scar formation depends on a plethora of factors. Given the impact of abnormal scar formation, interventions aimed to improve scar formation would be most advantageous. The tissue stromal vascular fraction (tSVF) of adipose tissue is composed of a heterogenous mixture of cells embedded in extracellular matrix. It contains growth factors and cytokines involved in wound-healing processes, eg, parenchymal proliferation, inflammation, angiogenesis, and matrix remodeling. The aim of this study was to investigate the hypothesis that tSVF reduces postsurgical scar formation. This prospective, double-blind, placebo-controlled, randomized trial was conducted between 2016 and 2020. Forty mammoplasty patients were enrolled and followed for 1 year. At the end of the mammoplasty procedure, all patients received tSVF in the lateral 5 cm of the horizontal scar of 1 breast and a placebo injection in the contralateral breast to serve as an intrapatient control. Primary outcome was scar quality measure by the Patient and Observer Scar Assessment Scale (POSAS). Secondary outcomes were obtained from photographic evaluation and histologic analysis of scar tissue samples. Thirty-four of 40 patients completed follow-up. At 6 months postoperation, injection of tSVF had significantly improved postoperative scar appearance as assessed by the POSAS questionnaire. No difference was observed at 12 months postoperation. No improvement was seen based on the evaluation of photographs and histologic analysis of postoperative scars between both groups. Injection of tSVF resulted in improved wound healing and reduced scar formation at 6 months postoperation, without any noticeable advantageous effects seen at 12 months.

ВЛИЯНИЕ МЕЗЕНХИМАЛЬНЫХ СТВОЛОВЫХ КЛЕТОК ЖИРОВОЙ ТКАНИ И ПАРАКРИННЫХ ФАКТОРОВ КОНДИЦИОННОЙ СРЕДЫ НА ЗАЖИВЛЕНИЕ ЛУЧЕВЫХ ЯЗВ ПРИ ТЕРАПИИ ТЯЖЕЛЫХ РАДИАЦИОННЫХ ПОРАЖЕНИЙ КОЖИ У КРЫС

Purpose: Studying of the effects transplantation of cultured mesenchymal stem cells of adipose tissue (MMSC) and adipose-derived stromal vascular fraction (SVF), as well as the introduction of paracrine factors (PF) of conditioned medium in an isolated or combined application for severe local radiation skin lesions in the experiment.&#x0D; Material and methods: Rats of the inbred Wistar–Kyoto strain were irradiated to local X-rays exposure in the iliolumbar region of the back at a dose of 110 Gy. The transplantation of cultured MMSC was performed twice at doses of 2.1 × 106 and 2.6 × 106 on the 28th and 35th days after irradiation. Adipose-derived SVF was administered at the same time in doses of 3.2 × 106 and 2.8 × 106, respectively. PF were administered five times from the 1st to the 10th day after irradiation. The severity of radiation damage to the skin and the effects of therapy were evaluated in dynamics by clinical manifestations, using planimetry and histological methods.&#x0D; Results: Radiation exposure with these parameters caused severe radiation injuries of the skin with non-healing ulcers formed by the 21–25th day after irradiation. The area of radiation ulcers in rats of the control group in the period from the 26th to the 83rd day slowly decreased from 2.76 ± 0.12 cm2 to 1.85 ± 0.13 cm2. In 50 % of the animals in the control group, ulcers persisted for more than 4 months after irradiation. In rats of the experimental groups, more intensive healing and a decrease in the area of radiation ulcers was noted. With isolated administration of cultured MMSC or SVF, a statistically significant decrease in the area of ulcers compared with the control was observed on the 104–125th day, and with the introduction of PF on the 83rd day after irradiation, p &lt;0.05. In the control group, by the118th day after irradiation, radiation ulcers healed only in 25 % of rats, and in the experimental groups with isolated administration of cultured MMSC, SVF and PF in 40–55 % of the rats showed complete epithelialization of wounds with the formation of an atrophic scar. Under the conditions of combined use of stem cells and conditioned medium factors, the number of animals with complete healing of radiation ulcers was 85–100 % by 118th days, p &lt;0.05.&#x0D; Conclusion: Thus, transplantation of cultured MMSC of adipose tissue and adipose-derived SVF, as well as the introduction of PF of conditioned medium, can enhance the regeneration processes and stimulate skin regeneration, promoting earlier healing of chronic radiation ulcers in severe local radiation injuries. Moreover, with the combined introduction of PF and adipose-derived stem cell transplantation, the effectiveness of the healing of radiation ulcers was increases.