Adipose-derived Stromal Vascular Fraction Research Articles

Abstract 10.55 PLATELET-RICH PLASMA VS. FETAL BOVINE SERUM IN ENGINEERING OF AXIALLY-VASCULARIZED OSTEOGENIC GRAFTS FROM HUMAN ADIPOSE-DERIVED CELLS TO TREAT AVASCULAR NECROSIS OF BONE

INTRODUCTION: Avascular necrosis of bone (AVN) leads to sclerosis and collapse of bone and joints. Engineered, axially vascularized, human adipose-derived stromal vascular fraction (SVF) cell based osteogenic constructs have been shown to revitalize necrotic bone of clinically-relevant size in a challenging rat model of AVN. To reduce regulatory difficulties towards clinical translation, fetal bovine serum (FBS) was substituted by thrombin-activated platelet-rich plasma (tPRP). METHODS: SVF cells from 5 lipoaspirate were isolated and cultured onto porous hydroxyapatite scaffolds within a perfusion-based bioreactor system for 5 days. The medium was supplemented either with 10% FBS or 10% tPRP. The resulting constructs were inserted into devitalized bone cylinders mimicking AVN-affected bone. A ligated vascular bundle was inserted upon subcutaneous implantation of constructs in nude rats. After 1 and 8 weeks, vascularization and bone formation were analyzed. RESULTS: After 1 week, neither maximal distance of vessels from the bundle nor vascular density was significantly different. However, FBS cultured grafts revealed significantly more human vessel (hCD34) and osteoclasts compared to tPRP cultured grafts. Overall macrophages and M2 macrophages were not different between FBS and tPRP cultured grafts. After 8 weeks in vivo, 3/5 samples from FBS culture and 1/5 sample from tPRP culture showed bone formation. Roughly 40% of the osteocytes were of human origin (36% from FBS and 42% from tPRP culture). DISCUSSION: Despite promising results in literature, replacement of FBS by tPRP resulted in a reduced capacity of bone formation in our series. Further studies are necessary to analyze and improve the low bone formation capacity, possibly caused by the heterogeneity of the SVF donors and tPRP samples.

Protection of human adipose stromal vascular fraction derived culture supernatant against acute renal ischemia/reperfusion injury

Objective To observe the effect of human adipose stromal vascular fraction (SVF) derived culture supernatant protecting kidney from acute ischemia/reperfusion injury (IRI). Methods SVF was isolated and was used for the preparation of SVF derived culture supernatant named SVF conditioned medium (SVF-CM). Hypoxia/reoxygenation (H/R) injury model of renal tubular epithelial cell (HK-2) was established for cell proliferation and apoptosis assay. Thirty-two SD rats were divided into four groups randomly: SVF-CM group, SVF group, control group, and sham group. Twenty-four hours after surgery, blood sample was collected for the detection of serum creatinine (SCr) and blood urea nitrogen (BUN). Kidney tissues were retrieved for hematoxylin and eosin (HE) and immunohistochemical staining. Results Both SVF-CM and SVF could significantly enhance the proliferative capability as well as attenuate the apoptosis of HK-2, while no significant difference could be found between the two groups for cell proliferation (P=0.781) and apoptosis (P=0.921, 0.280). At 24 h after surgery, serum levels of SCr and BUN in both SVF-CM and SVF groups were significantly lower than that in control group (P=0.000). However, there was no significant difference between the two groups (P=0.993, 0.985). Tubular damage score in both SVF-CM (1.9±0.8) and SVF (1.7±0.9) groups were significantly lower than that in control group (3.3±0.7) (P=0.000). Meanwhile, the numbers of proliferating cell nuclear antigen (PCNA) positive cells in both SVF-CM [(60.86±18.39) cells] and SVF [(62.51±20.03) cells] groups were significantly higher than that in control group [(33.61±6.91) cells] (P=0.000). Additionally, the numbers of terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) positive cells in both SVF-CM [(24.73±6.82) cells] and SVF [(22.11±5.68) cells] groups were significantly lower that in control group [(45.12±7.85) cells] (P=0.000). However, no significant difference on tubular damage score, number of proliferative cells and apoptotic cells could be found between SVF-CM and SVF groups (P=0.114, 0.875, 0.197). Conclusion Administration of SVF derived culture supernatant or SVF was equally effective in promoting the structural and functional recovery of damaged kidney. Key words: Adipose stromal vascular fraction; Culture supernatant; Acute kidney injury; Ischemia/reperfusion injury

78 - Adipose stromal vascular fraction and adipose stem cells markedly decrease inflammation and alter immune cell frequencies in a murine model of multiple sclerosis

78 - Adipose stromal vascular fraction and adipose stem cells markedly decrease inflammation and alter immune cell frequencies in a murine model of multiple sclerosis

253 - Comparison of human adipose stromal vascular fraction and adipose-derived mesenchymal stem cells for the attenuation of acute renal ischemia/reperfusion injury

Stem cells therapy has been suggested as a promising option for the treatment of acute kidney injury (AKI). This study was performed to compare the abilities of xenogenic transplantation of human adipose stromal vascular fraction (SVF) and adipose-derived mesenchymal stem cells (AdMSCs) to facilitate the recovery of renal function and structure in a rat model of ischemia/reperfusion (IR) induced AKI. SVF or AdMSCs were transplanted to the injured kidney through intra-parenchymal injection. Significantly improved renal function and reduced tubular injury were observed in SVF and AdMSCs groups. Administration of SVF or AdMSCs contributed to significantly improved cell proliferation and markedly reduced cell apoptosis in parallel with reduced microvascular rarefaction in injured kidney. IR injury resulted in higher levels of inflammatory cytokines, whereas xenogenic transplantation of SVF or AdMSCs reduced but not induced inflammatory cytokines expression. Additionally, in vitro study showed that administration of SVF or AdMSCs could also significantly promote the proliferation and survival of renal tubular epithelial cells underwent hypoxia/reoxygenation injury through secreting various growth factors. However, cell proliferation was significantly promoted in SVF group than in AdMSCs group. In conclusion, our study demonstrated that administration of SVF or AdMSCs was equally effective in attenuating acute renal IR injury.

106 - Isolation of adipose stromal vascular fraction and adipose derived stem cells from defferent donor age, sites and sex using 5 year data

106 - Isolation of adipose stromal vascular fraction and adipose derived stem cells from defferent donor age, sites and sex using 5 year data

Accelerated Healing of a Diabetic Foot Ulcer Using Autologous Stromal Vascular Fraction Suspended in Platelet-Rich Plasma

We describe the case of a Type I diabetic patient with a refractory foot ulcer that remained unhealed for 2 years despite conventional therapy. Autologous adipose-derived stromal vascular fraction suspended in autologous platelet-rich plasma was applied to the wound, which completely healed within 1 month. The wound remained closed with no complications for a 2-year follow-up. Reporting of this and similar cases may lead to larger clinical trials that will prove the efficacy of this therapy that may offer accelerated healing and lessen the financial burden of more expensive therapeutic modalities.

Adipose stromal vascular fraction attenuates TH1 cell-mediated pathology in a model of multiple sclerosis

BackgroundThe therapeutic efficacy of adipose-derived stem cells (ASCs) has been investigated for numerous clinical indications, including autoimmune and neurodegenerative diseases. Less is known using the crude adipose product called stromal vascular fraction (SVF) as therapy, although our previous studies demonstrated greater efficacy at late-stage disease compared to ASCs in the experimental autoimmune encephalomyelitis (EAE) mouse, a model of multiple sclerosis. In this study, SVF cells and ASCs were administered during the pathogenic progression, designated as early disease, to elucidate immunomodulatory mechanisms when high immune cell activities associated with autoimmune signaling occur. These implications are essential for clinical translation when considering timing of administration for cell therapies.MethodsWe investigated the effects of SVF cells and ASCs by analyzing the spleens, peripheral blood, and central nervous system tissues throughout the course of EAE disease following administration of SVF cells, ASCs, or vehicle. In vitro, immunomodulatory potentials of SVF cells and ASCs were measured when exposed to EAE-derived splenocytes.ResultsInterestingly, treatment with SVF cells and ASCs transiently enhanced the severity of disease directly after administration, substantiating this critical immunomodulatory signaling. More importantly, it was only the EAE mice treated with SVF cells that were able to overcome the advancing pathogenesis and showed improvements by the end of the study. The frequency of lesions in spinal cords following SVF treatment correlated with diminished activities of the T helper type 1 cells, known effector cells of this disease. Co-cultures with splenocytes isolated from EAE mice revealed transcripts of interleukin-10 and transforming growth factor-β, known promoters of regulatory T cells, that were greatly expressed in SVF cells compared to ASCs, and expression levels of signaling mediators related to effector T cells were insignificant in both SVF cells and ASCs.ConclusionThis is the first evidence, to date, to elucidate a mechanism of action of SVF treatment in an inflammatory, autoimmune disease. Our data supports key immunomodulatory signaling between cell therapies and T cells in this T cell-mediated disease. Together, treatment with SVF mediated immunomodulatory effects that diminished effector cell activities, promoted regulatory T cells, and reduced neuroinflammation.

Clinical application of adipose-derived stromal vascular fraction in 3 Thoroughbred horses with superficial digital flexor tendonitis: Case Report

Tendon injuries are considered major causes of wastage in active Thoroughbred racehorses as they are among the most common musculoskeletal injuries in equine athletes. There has been considerable interest in the potential use of concentrated adipose tissue digest, such as stromal vascular fraction, in tendon overstrain injuries. It has been reported that the adipose-derived stem cells, which are present in stromal vascular fraction of adipose tissue, can promote neovascularization and improve healing process. The purpose of this study was to evaluate the potential effects of intralesional use of autologous adipose-derived stromal vascular fraction on tendon healing in three Thoroughbred active racehorses with moderate to severe superficial digital flexor tendonitis. Based on the results of this report it seems that intratendinous injection of autologous adipose-derived stromal vascular fraction leads to marked clinical improvement and reduction of rehabilitation period in racehorses suffering from superficial digital flexor tendonitis.

First clinical case report of local microinjection of autologous fat and adipose-derived stromal vascular fraction for perianal fistula in Crohn\u2019s disease

Mesenchymal stem cell therapy is a promising treatment for perianal Crohn’s fistulas refractory to conventional therapy, which are an extremely morbid complication and a true therapeutic challenge. Autologous adipose-derived stromal vascular fraction (ADSVF) is an easily accessible source of cells with angiogenic, anti-inflammatory, immunomodulatory, and regenerative properties. Here, we describe a case involving a patient with severe perianal Crohn’s fistulas refractory to the best medical and surgical practices who received local treatment with ADSVF and microfat. This patient was first examined under anesthesia with drainage via seton placement; 1 week later, on a single day, he underwent adipose tissue extraction, ADSVF and microfat preparation, and the local injection of 14 ml of microfat and approximately 20 million viable ADSVF cells into the soft tissue around the fistulas. No serious adverse events were observed. At the first endpoint at 12 weeks, the fistula had clinically healed with complete re-epithelialization of all external openings; no fistula tract was detected on magnetic resonance imaging, confirming this finding. This good clinical outcome was sustained at 48 weeks and was associated with a reduction in the severity of perianal disease and an improvement in quality of life. The current case highlights the therapeutic potential of a new cellular treatment for Crohn’s patients with refractory perianal fistulas based on the innovative hypothesis that the combined action of ADSVF in association with the trophic characteristics of a microfat graft could be beneficial for this condition.Trial registration: EudraCT number 201325, NCT02520843. Registered on 5 August 2015

Magnetic Resonance Imaging and Biomechanical Analysis of Adipose-derived Stromal Vascular Fraction Applied on Rotator Cuff Repair in Rabbits.

Background:Adipose-derived stromal vascular fraction (ADSVF) can be applied to repair tendon and ligament tears. ADSVF treatment has a better therapeutic potential than adipose stem cells alone in promoting the healing of connective tissue injury in rabbit models. Magnetic resonance imaging (MRI) and biomechanical testing were used in this study to evaluate the efficiency of SVF in the healing of tendon-bone interface of a rotator cuff injury after reattachment.Methods:A total of 36 rabbits were studied between March and June 2016, 18 rabbits received the SVF-fibrin glue (SVF-FG) treatment and the other 18 formed the control group. ADSVF was isolated from each rabbit. A bilateral amputation of the supraspinatus tendon and parallel reconstruction was also performed on all the 36 rabbits. Then, a mixture of SVF and FG was injected into the tendon-bone interface of the SVF-FG group, whereas the control group only received FG. The animals were randomly sacrificed at 4, 8, and 12 weeks after surgery (n = 6 per group), respectively. The shoulders were prepared for MRI scanning and analysis of biomechanical properties. Analyses of variance were performed using SPSS 13.0.Results:MRI scanning showed that the signal-to-noise quotient of the SVF-FG group was not significantly higher than that of the control group at either 4 (20.1 ± 3.6 vs. 18.2 ± 3.4, F = 1.570, P = 0.232) or 8 weeks (20.7 ± 3.3 vs. 18.0 ± 3.0, F = 2.162, P = 0.117) posttreatment, and only became significant after 12 weeks (27.5 ± 4.6 vs. 22.1 ± 1.9, F = 4.968, P = 0.009). Biomechanical properties such as the maximum load, maximum strength, and the stiffness for the SVF-FG group were significantly greater than that for the control group at 8 weeks’ posttreatment (maximum load: 166.89 ± 11.62 N vs. 99.40 ± 5.70 N, P < 0.001; maximum strength: 8.22 ± 1.90 N/mm vs. 5.82 ±0.68 N/mm, P < 0.010; and the stiffness: 34.85± 3.00 Pa vs. 24.57± 5.72 Pa, P < 0.010).Conclusion:Local application of ADSVF might lead to better tendon-bone healing in rabbit models.

Adipose-Derived Stromal Vascular Fraction/Xenohybrid Bone Scaffold: An Alternative Source for Bone Regeneration.

Adipose tissue-derived stem cells (ASCs) are a promising tool for the treatment of bone diseases or skeletal lesions, thanks to their ability to potentially repair damaged tissue. One of the major limitations of ASCs is represented by the necessity to be isolated and expanded through in vitro culture; thus, a strong interest was generated by the adipose stromal vascular fraction (SVF), the noncultured fraction of ASCs. SVF is a heterogeneous cell population, directly obtained after collagenase treatment of adipose tissue. In order to investigate and compare the bone-regenerative potential of SVF and ASCs, they were plated on SmartBone®, a xenohybrid bone scaffold, already used in clinical practice with successful results. We showed that SVF plated on SmartBone, in the presence of osteogenic factors, had better osteoinductive capabilities than ASCs, in terms of differentiation into bone cells, mineralization, and secretion of soluble factors stimulating osteoblasts. Indeed, we observed an increasing area of new tissue over time, with and without OM. These data strongly support an innovative idea for the use of adipose SVF and bone scaffolds to promote tissue regeneration and repair, also thanks to an easier cell management preparation that allows a potentially larger use in clinical applications.

Isolation of Murine Adipose-Derived Stromal/Stem Cells for Adipogenic Differentiation or Flow Cytometry-Based Analysis.

Murine models of obesity or reduced adiposity are a valuable resource for understanding the role of adipocyte dysfunction in metabolic disorders. Adipose tissue stromal vascular cells or primary adipocytes derived from murine adipose tissue and grown in culture are essential tools for studying the mechanisms underlying adipocyte development and function. Herein, we describe methods for the isolation, expansion, and long-term storage of murine adipose-derived stromal/stem cells along with protocols for inducing adipogenesis in this cell population or isolating the adipose stromal vascular fraction cells for flow cytometric analysis.

Autologous and heterotopic transplantation of adipose stromal vascular fraction ameliorates stress urinary incontinence in rats with simulated childbirth trauma.

IntroductionAutologous transplantation of adipose stromal vascular fraction (SVF) is a cost-effective and technically accessible option for cell therapy. Clinical study of SVF transplantation for male stress urinary incontinence (SUI) is underway, but the effectiveness remains unknown for female SUI, majority of which is caused by childbirth trauma.MethodsVaginal Distension (VD) rats were generated as in vivo model for female SUI. To quantitate the severity of SUI, leak point pressure (LPP) was measured by placing a bladder catheter. There was a characteristic waveform of LPP with two-peaks, and we counted the second peak as an LPP value. Adipose SVF was separated from inguinal fat and delivered into external urethral sphincter (EUS) through transperineal injection. LPP was measured 7 or 14 days after SVF transplantation. Tissue damage and collagen synthesis around the EUS were visualized by Masson's trichrome and eosin staining. Antibody against α-smooth muscle actin (α-SMA) was used to stain smooth muscle or activated stromal cells. Donor SVF cells were distinguished from recipient EUS tissue by tracking with GFP transgene.ResultsVD procedure decreased the frequency at which the normal LPP waveform appeared and lowered the LPP value. SVF injection normalized the waveform as well as the level of LPP. VD disrupted histological structure of EUS and SVF failed to differentiate into striatal muscles. Instead, SVF increased α-SMA positive cells and collagen synthesis but the phenomena depended on VD stimulus. GFP tracking indicated that the transplanted SVF cells persisted for four weeks and synthesized α-SMA protein simultaneously.ConclusionsAutologous transplantation of adipose SVF displayed bulking effects through collagen synthesis. However, such heterotopic activation was dependent on tissue damage.

Vasculogenic and angiogenic potential of adipose stromal vascular fraction cell populations in vitro

Adipose-derived stromal vascular fraction (SVF) is a heterogeneous cell source that contains endothelial cells, pericytes, smooth muscle cells, stem cells, and other accessory immune and stromal cells. The SVF cell population has been shown to support vasculogenesis in vitro as well vascular maturation in vivo. Matrigel, an extracellular matrix (ECM) mixture has been utilized in vitro to evaluate tube formation of purified endothelial cell systems. We have developed an in vitro system that utilizes freshly isolated SVF and ECM molecules both in pure form (fibrin, laminin, collagen) as well as premixed form (Matrigel) to evaluate endothelial tip cell formation, endothelial stalk elongation, and early stages of branching and inosculation. Freshly isolated SVF rat demonstrate cell aggregation and clustering (presumptive vasculogenesis) on Matrigel ECM within the first 36 h of seeding followed by tip cell formation, stalk cell formation, branching, and inosculation (presumptive angiogenesis) during the subsequent 4 days of culture. Purified ECM molecules (laminin, fibrin, and collagen) promote cell proliferation but do not recapitulate events seen on Matrigel. We have created an in vitro system that provides a functional assay to study the mechanisms of vasculogenesis and angiogenesis in freshly isolated SVF to characterize SVF’s blood vessel forming potential prior to clinical implantation.

Hand and wrist joint procedures in sclerodermic patients – a systematic review

Hand reconstructive surgery in systemic sclerosis has long time been considered a taboo due to the frequent global stiffness and menaced wound healing associated with digital ischemia and skin tightness. We assumed that joint procedures to sclerodermic hands or wrists have not a higher rate of infection, wound healing problem or non-union in comparison to non-sclerodermic population. We systematically reviewed the literature assessing these complications after performing joint reconstruction in hands and wrists of sclerodermic patients. Studies were identified through systematic review of the available literature in the Pubmed Medline, Cochrane Central Register of Controlled Trials, Embase, Web of Science database up to May 3rd, 2017. Database was searched using a set of search terms, which described systemic sclerosis, bone and joint surgery, and hand or wrist surgery. Only studies including joint procedures in hands or wrists of sclerodermic patients that were related to the functional outcomes and morbidity after surgery were selected. Reviews were excluded. Studies relevant to soft tissue reconstruction in sclerodermic hands or wrists, such as digital sympathectomy, autologous adipose-derived stromal vascular fraction, vascular reconstruction or management of finger ulcers were also excluded. Results A total of 265 unique articles were identified in PubMed. Thirty-eight titles selected for abstract review. Twenty-nine abstracts did not meet the inclusion criteria or did not evaluate our predefined endpoint and were excluded. Nine articles were fully read and two more articles were considered irrelevant and excluded. Seven studies were deemed eligible for our systematic review. One hundred and sixteen sclerodermic patients were found. A total of 402 joint procedures in sclerodermic hand and wrist were exported. The operations concerned metacarpophalangeal and interphalangeal arthroplasty, joint replacement or fusion, Kapandji procedures, osteotomy of the finger and removal of the hardware. A low complications rate in terms of infection or digital ischemia after surgery was mentioned to all studies. In most of the cases, wound healing was uneventful and only in some cases, it was described slow. In cases of joint fusion, bone healing was successfully achieved. The functional outcome was reliable in all the cases. The wrist and hand joint procedures in systemic sclerosis were found to be reliable and related to low morbidity in terms of infection rate, wound healing and bone union. Results from future studies will unquestionably contribute to further establishment of knowledge about the therapeutic outcome after surgery in these suboptimal conditions of the sclerodermic hand.

Engineering of an angiogenic niche by perfusion culture of adipose-derived stromal vascular fraction cells

In vitro recapitulation of an organotypic stromal environment, enabling efficient angiogenesis, is crucial to investigate and possibly improve vascularization in regenerative medicine. Our study aims at engineering the complexity of a vascular milieu including multiple cell-types, a stromal extracellular matrix (ECM), and molecular signals. For this purpose, the human adipose stromal vascular fraction (SVF), composed of a heterogeneous mix of pericytes, endothelial/stromal progenitor cells, was cultured under direct perfusion flow on three-dimensional (3D) collagen scaffolds. Perfusion culture of SVF-cells reproducibly promoted in vitro the early formation of a capillary-like network, embedded within an ECM backbone, and the release of numerous pro-angiogenic factors. Compared to static cultures, perfusion-based engineered constructs were more rapidly vascularized and supported a superior survival of delivered cells upon in vivo ectopic implantation. This was likely mediated by pericytes, whose number was significantly higher (4.5-fold) under perfusion and whose targeted depletion resulted in lower efficiency of vascularization, with an increased host foreign body reaction. 3D-perfusion culture of SVF-cells leads to the engineering of a specialized milieu, here defined as an angiogenic niche. This system could serve as a model to investigate multi-cellular interactions in angiogenesis, and as a module supporting increased grafted cell survival in regenerative medicine.

The effect of adipose derived stromal vascular fraction on stasis zone in an experimental burn model

BackgroundStasis zone is the surrounding area of the coagulation zone which is an important part determining the extent of the necrosis in burn patients. In our study we aim to salvage the stasis zone by injecting adipose derived stromal vascular fraction (ADSVF). MethodsThermal injury was applied on dorsum of Sprague–Dawley rats (n=20) by the “comb burn” model as described previously. When the burn injury was established on Sprague–Dawley rats (30min); rat dorsum was separated into 2 equal parts consisting of 4 burn zones (3 stasis zone) on each pair. ADSVF cells harvested from inguinal fat pads of Sprague–Dawley rats (n=5) were injected on the right side while same amount of phosphate buffered saline (PBS) injected on the left side of the same animal. One week later, average vital tissue on the statis zone was determined by macroscopy, angiography and microscopy. Vascular density, inflammatory cell density, gradient of fibrosis and epithelial thickness were determined via immunohistochemical assay. ResultsMacroscopic stasis zone tissue viability (32±3.28%, 57±4.28%) (p<0.01), average number of vessels (10.28±1.28, 19.43±1.72) (p<0.01), capillary count (15.67±1.97, 25.35±2.15) (p<0.01) vascular density (1.55±0.38, 2.14±0.45) (p<0.01) epithelial thickness (0.014±0.009mm, 0.024±0.0011mm) were higher on ADSVF side. Fibrosis gradient (1.87±0.51, 1.50±0.43) (p<0.01) and inflammatory cell density (1.33±0.40, 1.20±0.32) (p<0.01) were higher on the PBS side. ConclusionMacroscopic and microscopic findings determined that ADSVF has a statistically significant benefit for salvaging stasis zone on acute burn injuries.

SAFETY AND EFFECTIVENESS OF INTRAARTICULAR ADMINISTRATION OF ADIPOSE-DERIVED STROMAL VASCULAR FRACTION FOR TREATMENT OF KNEE ARTICULAR CARTILAGE DEGENERATIVE DAMAGE: PRELIMINARY RESULTS OF A CLINICAL TRIAL

The incidence of knee osteoarthritis tends to increase every year and constitutes more than 83% of overall OA morbidity. Moreover, the OA morbidity among younger patients is also increasing. However, currently available treatment methods do not provide quite satisfactory outcomes.Purpose of the study – to evaluate safety and efficacy of intraarticular introduction of autologous adipose-derived stromal vascular fraction for treatment of knee osteoarthritis.Material and methods. By the moment of writing the present report, 28 patients were included into the study. All patients underwent tumescent liposuction under local anesthesia. The stromal vascular fraction was isolated from lipoaspirate within 1,5 hours after harvesting and subsequently injected into the articular cavity. Follow-up period was 6 months after injections. The authors report on efficacy data of 10 patients who completed the study according to protocol and safety data of all 28 patients. Efficacy was evaluated basing on laboratory assessments and patient’s subjective assessment by validated questionnaires.Results. Neither adverse reactions no adverse events were observed. Significant decrease of pain severity by VAS was noted in one week after injection and pain score continued decreasing during the whole follow up period. The increase of KOOS score was noted starting on the fifth week after injection. KSS part 1 score increased in 8 weeks, KSS part 2 score — in 6 months after injection. Physical health, assessed with SF-36 questionnaire significantly improved in 2 and 6 months after the procedure. There was a clear trend towards improvement of mental health.Conclusion. Preliminary results of clinical study suggest intraarticular injection of autologous adipose-derived stromal vascular fraction to be a safe and efficient method of the treatment of knee osteoarthritis.

Formation of Adipose Stromal Vascular Fraction Cell-Laden Spheroids Using a Three-Dimensional Bioprinter and Superhydrophobic Surfaces.

The therapeutic infusion of adipose-derived stromal vascular fraction (SVF) cells for the treatment of multiple diseases, has progressed to numerous human clinical trials; however, the often poor retention of the cells following implantation remains a common drawback of direct cell injection. One solution to cellular retention at the injection site has been the use of biogels to encapsulate cells within a microenvironment before and upon implantation. The current study utilized three-dimensional bioprinting technology to evaluate the ability to form SVF cell-laden spheroids with collagen I as a gel-forming biomatrix. A superhydrophobic surface was created to maintain the bioprinted structures in a spheroid shape. A hydrophilic disc was printed onto the hydrophobic surface to immobilize the spheroids during the gelation process. Conditions for the automated rapid formation of SVF cell-laden spheroids were explored, including time/pressure relationships for spheroid extrusion during bioprinting. The formed spheroids maintain SVF viability in both static culture and dynamic spinner culture. Spheroids also undergo a time-dependent contraction with the retention of angiogenic sprout phenotype over the 14-day culture period. The use of a biphilic surface exhibiting both superhydrophobicity to maintain the spheroid shape and a hydrophilicity to immobilize the spheroid during gel formation produces SVF cell-laden spheroids that can be immediately transplanted for therapeutic applications.

Immunomodulatory Effects of Adipose Stromal Vascular Fraction Cells Promote Alternative Activation Macrophages to Repair Tissue Damage.

The pathogenesis of many diseases is driven by the interactions between helper T (TH ) cells and macrophages. The phenotypes of these cells are functional dichotomies that are persuaded according to the surrounding milieu. In both multiple sclerosis and the experimental autoimmune encephalomyelitis (EAE) model, TH 1 and TH 17 cells propagate autoimmune signaling and inflammation in the peripheral lymphoid tissues. In turn, this proinflammatory repertoire promotes the classical activation, formerly the M1-type, macrophages. Together, these cells infiltrate into the central nervous system (CNS) tissues and generate inflammatory and demyelinating lesions. Our most recent report demonstrated the immunomodulatory and anti-inflammatory effects of adipose stromal vascular fraction (SVF) cells and adipose-derived stem cells (ASCs) that led to functional, immunological, and pathological improvements in the EAE model. Here, a deeper investigation revealed the induction of regulatory T cells and alternative activation, or M2-type, macrophages in the periphery followed by the presence of alternative activation macrophages, reduced cellular infiltrates, and attenuation of neuroinflammation in CNS tissues following intraperitoneal administration of these treatments. Spleens from treated EAE mice revealed diminished TH 1 and TH 17 cell activities and were markedly higher in the levels of anti-inflammatory cytokine interleukin-10. Interestingly, SVF cells were more effective than ASCs at mediating these beneficial changes, which were attributed to their localization to the spleens after administration. Together, SVF cells rapidly and robustly attenuated the propagation of autoimmune signaling in the periphery that provided a permissive milieu in the CNS for repair and possibly regeneration. Stem Cells 2017;35:2198-2207.