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-1ß and IL-10 by SVF cells isolated from subcutaneous adipose tissue (SAT), while in mesenteric adipose tissue (MAT) SVF cell cultures only IL-1ß 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.

Evaluation of the effects of adding an adipose tissue-derived stromal vascular fraction to platelet-rich plasma injection in the treatment of androgenetic alopecia: A randomized clinical trial.

BACKGROUND: Stromal vascular fraction (SVF) cells derived from adipose tissue and platelet-rich plasma (PRP) are among novel treatments for androgenetic alopecia (AGA). We aimed to investigate the effect of adding SVF to PRP and compare it to administering PRP injection alone. METHODS: Eighteen patients were randomly divided into two groups of nine. The PRP group was treated with PRP at all three visits at 1-month intervals, while the SVF-PRP group received an SVF injection on the first visit and a PRP injection on the second and third visits. Each group was evaluated at baseline and 20 weeks after the therapy's initiation. RESULTS: Changes in mean hair diameter and hair count compared to baseline were significant in both groups. The PRP group experienced a greater increase in mean hair count than the SVF-PRP group, and the SVF-PRP group had a marginally greater increase in hair diameter than the PRP group. These differences were not statistically significant compared to each other. The patient and physician assessment scores exceeded the mean (on a scale from 0: poor to 3: excellent) in both groups. CONCLUSION: Adding one SVF injection to two PRP treatment sessions versus three PRP injections alone had no significant difference in evaluated variables. If additional research demonstrates the same results, we suggest that multiple SVF injection sessions may be required to produce a statistically significant difference compared to PRP injection alone. Moreover, considering lower cost and greater accessibility of PRP, it can be used before SVF in the treatment of AGA.

Clinical Evaluation of Safety and Efficacy of a Central Current Good Manufacturing Practices Laboratory Produced Autologous Adipose-Derived Stromal Vascular Fraction Cell Therapy Product for the Treatment of Knee Osteoarthritis.

Knee osteoarthritis (KOA) is a prevalent condition characterized by the progressive deterioration of the entire joint and has emerged as a prominent contributor to disability on a global scale. The nature of the disease and its impact on joint function significantly limit mobility and daily activities, highlighting its substantial influence on patients' overall well-being. Stromal vascular fraction (SVF) is a heterogenous, autologous cell product, containing mesenchymal stem cells, derived from the patient's subcutaneous adipose tissue with demonstrated safety and efficacy in the treatment of KOA patients. We conducted a single-arm, open-label, multisite, FDA approved clinical study in Kellgren-Lawrence severity grade 2-4 KOA patients. The cellular product was manufactured from patient-specific lipoaspirate in a centrally located FDA-compliant manufacturing facility. Twenty-nine subjects were treated with a quality tested single intra-articular injection of GMP manufactured SVF. Adverse events, laboratory values, vital signs, and physical examination findings were monitored during the study period. Robust tolerability, without any substantial safety issues, was demonstrated. Knee pain and function, assessed through the Knee Injury and Osteoarthritis Outcome Score (KOOS), demonstrated notable improvements. These positive benefits persisted for up to 12 months, and the majority of participants expressed satisfaction. SVF from each patient was stored in a liquid nitrogen freezer for future clinical treatments. Unique to this study of autologous cells is the shipment of lipoaspirate from the clinic to a central FDA-compliant manufacturing facility for cleanroom-controlled manufacturing. The cell product characterization data demonstrate that this method produces an equivalent product in terms of cell count and viability with the added benefit of further quality assurance testing, including sterility, endotoxin, and flow cytometry, before patient administration. Clinical Trial Registration Number: NCT04043819.

Combined laser-activated SVF and PRP remodeled spinal sclerosis via activation of Olig-2, MBP, and neurotrophic factors and inhibition of BAX and GFAP.

A single injection of platelet-rich plasma (PRP) or stromal vascular fraction (SVF) in treating neurological ailments suggests promise; however, there is limited evidence of the efficacy of combination therapy. This trial aimed to determine whether combining SVF and PRP could provide further therapeutic effects in treating multiple sclerosis (MS). Fifteen Persian cats were separated into three groups (n = 5): group I (control negative), and group II (control positive); EB was injected intrathecally into the spinal cord and then treated 14 days later with intrathecal phosphate buffered saline injection, and group III (SVF + PRP), cats were injected intrathecally with EB through the spinal cord, followed by a combination of SVF and PRP 14 days after induction. Therapeutic effects were evaluated using the Basso-Beattie-Bresnahan scale throughout the treatment timeline and at the end. Together with morphological, MRI scan, immunohistochemical, transmission electron microscopy, and gene expression investigations. The results demonstrated that combining SVF and PRP successfully reduced lesion intensity on gross inspection and MRI. In addition to increased immunoreactivity to Olig2 and MBP and decreased immunoreactivity to Bax and GFAP, there was a significant improvement in BBB scores and an increase in neurotrophic factor (BDNF, NGF, and SDF) expression when compared to the positive control group. Finally, intrathecal SVF + PRP is the most promising and safe therapy for multiple sclerosis, resulting in clinical advantages such as functional recovery, MRI enhancement, and axonal remyelination.

Efficacy of the immediate adipose-derived stromal vascular fraction autograft on functional sensorimotor recovery after spinal cord contusion in rats.

BACKGROUND: Spinal cord injuries (SCI) lead to functional alteration with important consequences such as motor and sensory disorders. The repair strategies developed to date remain ineffective. The adipose tissue-derived stromal vascular fraction (SVF) is composed of a cocktail of cells with trophic, pro-angiogenic and immunomodulatory effects. Numerous therapeutic benefits were shown for tissue reconstitution, peripheral neuropathy and for the improvement of neurodegenerative diseases. Here, the therapeutic efficacy of SVF on sensorimotor recovery after an acute thoracic spinal cord contusion in adult rats was determined. METHOD: Male Sprague Dawley rats (n = 45) were divided into 3 groups: SHAM (without SCI and treatment), NaCl (animals with a spinal lesion and receiving a saline injection through the dura mater) and SVF (animals with a spinal lesion and receiving a fraction of fat removed from adipocytes through the dura mater). Some animals were sacrificed 14 days after the start of the experiment to determine the inflammatory reaction by measuring the interleukin-1ß, interleukin-6 and Tumor Necrosis Factor-α in the lesion area. Other animals were followed once a week for 12 weeks to assess functional recovery (postural and locomotor activities, sensorimotor coordination). At the end of this period, spinal reflexivity (rate-dependent depression of the H-reflex) and physiological adjustments (ventilatory response to metabosensitive muscle activation following muscle fatigue) were measured with electrophysiological tools. RESULTS: Compared to non-treated animals, results indicated that the SVF reduced the endogenous inflammation and increased the behavioral recovery in treated animals. Moreover, H-reflex depression and ventilatory adjustments to muscle fatigue were found to be comparable between SHAM and SVF groups. CONCLUSION: Our results highlight the effectiveness of SVF and its high therapeutic potential to improve sensorimotor functions and to restore the segmental sensorimotor loop and the communication between supra- and sub-lesional spinal cord regions after traumatic contusion.

Clinical efficacy of stromal vascular fraction gel in the treatment of mature striae distensae.

BACKGROUND: Striae Distensae (SD) is a common dermatological lesion. The mechanism of formation is unclear, the prevailing theory is mechanical pulling of the skin and hormonal changes. Traditional SD treatment methods include topical drugs, photoelectric therapy, stripping and others, but each has limitations. Stromal vascular fraction gel (SVF-gel) is a filler physically prepared from granular fat, enriched with adipose-derived stem cells (ADSCs) and extracellular matrix (ECM). A good effect in the treatment of neck lines, wounds, acne, and other aspects. SD formation and treatment goals are comparable to those of neck lines. In this study, SVF-gel filling will be used to treat mature SD, and its effectiveness and safety will be discussed in detail. METHODS: From December 2019 to June 2022, recruit patients who want to treat SD caused by obesity or pregnancy among those who have "autologous fat aspiration" to change their body shape. Preoperatively, the area to be treated for SD was marked, autologous fat aspiration was performed, and the aspirated fat was prepared as SVF-gel and filled into the preoperatively marked SD. All patients had preoperative and postoperative follow-up with planar photographs and VISIA skin analyzer photographs to assess surgical results and safety from subjective and objective perspectives. RESULTS: A total of 36 patients were enrolled, with 31 of them successfully followed up on. The mean Global Aesthetic Improvement Scale (GAIS) score six months after surgery was 1.87 ± 0.03. At six months postoperatively, the overall patient satisfaction rate was 90%. The depth, area, and color of SD improved six months after surgery, and no serious complications occurred in any of the patients. CONCLUSIONS: SVF-gel is a safe and effective method of improving mature SD and can be used as a clinical treatment option.

Autologous point-of-care stromal vascular fraction transplantation in dogs with advanced osteoarthritis of the knee and hip joints.

OBJECTIVE: The aim of the study was to assess lameness in dogs with advanced osteoarthritis of the hip and knee joints after a single autologous point-of-care transplantation of the Stromal Vascular Fraction (SVF) into the affected joint. MATERIALS AND METHODS: During a minilaparotomy, 10 g of falciform fat was removed from each patient for each joint to be treated. A modern and time-saving procedure (ARC TM System, InGeneron GmbH, Houston, USA) was used for the in-house preparation of the SVF, so that the isolated cells could be applied to the respective joint within 2 h after fat removal. In total, five knee joints of five patients and seven hip joints of four patients were treated. RESULTS: Improvement in lameness according to owner questionnaires was seen in 3 of 5 patients with knee joint arthritis and 2 of 4 patients with hip joint arthritis. Based on gait analysis, only one dog with gonarthrosis and one dog with coxarthrosis showed improvement up to a maximum of 3 months after surgery. CONCLUSION: This is the first case series on the treatment of osteoarthrosis of the knee or hip joint using point-of-care transplantation of the SVF. In individual cases, this method may represent a therapeutic approach for the treatment in dogs with advanced cox- or gonarthrosis, although only a short-term effect can be expected, which calls into question the effort and costs involved.

Stromal Vascular Fraction Gel (SVF-Gel) Combined with Nanofat for Tear Trough Deformity.

BACKGROUND: Tear trough deformity makes patients appear tired. Patients with less severe tear trough deformity prefer a less invasive method to correct the deformity. The infraorbital area is a multilayered tissue, and the aging of various components leads to tear trough deformity. To this end, we utilized the different characteristics of different fat derivatives to correct tear trough deformity. METHODS: Thirty-two patients with Barton Grade I/II tear trough deformity were enrolled in this study between September 2020 and March 2021. We injected Stromal Vascular Fraction Gel (SVF-Gel) into the suborbicularis oculi fat layer and Nanofat into the subcutaneous. After 12 months of follow-up, we evaluated the changes using standardized clinical photogrammetric techniques, volume, global aesthetic improvement scale, and patient self-evaluation. RESULTS: There were no major complications in any of the 32 patients. The measured data points demonstrated improvements in all aesthetic parameters. The width of the tear trough and the distance from the pupil to the tear trough improved. The Global Aesthetic Improvement Scale (GAIS) showed a high score (2.45±0.64 points), with patient self-assessment showing satisfactory results. CONCLUSION: SVF-Gel combined with Nanofat injection can effectively correct tear trough deformities. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Comparison research on the therapeutic effects of botulinum toxin type A and stromal vascular fraction gel on hypertrophic scars in the rabbit ear model.

BACKGROUND AND OBJECTIVES: Botulinum toxin type A (BTA) is often used for wrinkles and muscle convulsive diseases due to its blocking of the transmission of nerve impulses. Stromal vascular fraction gel (SVF-gel) prepared from adipose tissue has novel effects on skin depression and poor texture. Both BTA and SVF-gel are proved to possess anti-scar potential. This study aimed to assess and compare their therapeutic effects on hypertrophic scars. MATERIALS AND METHODS: The rabbit ear scar model was established and treated with BTA and SVF-gel, alone or in combination. Gross evaluation using Manchester Scar Scale (MSS) was conducted immediately, 4 and 8 weeks after initial treatment. After tissue sample harvest, histological and Western blot analyses were performed. RESULTS: All the treatments alleviated scar hyperplasia in different degrees by inhibiting fibroblast activation (Ki-67, α-SMA), tissue inflammation (CD45, IL-1ß) and the transforming growth factor-ß1 (TGF-ß1)/Smad3 pathway. Despite an excellent anti-inflammatory effect, improvement of scar appearance and pathological characteristics in SVF-gel-contained groups was not as good as that in BTA-only group, which might be related to the retention of M2-type macrophages (CD163 +) and partial maintenance of TGF-ß1 expression. CONCLUSION: Our data suggest that BTA has better anti-scar efficacy than SVF-gel, and the combination of these two treatments shows no obvious combinatorial effect.

A systematic review of the efficacy, safety and satisfaction of regenerative medicine treatments, including platelet-rich plasma, stromal vascular fraction and stem cell-conditioned medium for hypertrophic scars and keloids.

The primary objective of this study is to examine the efficiency of various regenerative medicine approaches, such as platelet-rich plasma, cell therapy, stromal vascular fraction, exosomes and stem cell-conditioned medium, in the process of healing hypertrophic and keloid scars. Major databases including PubMed, Scopus and Web of Science were systematically searched, and based on the content of the articles and the inclusion and exclusion criteria, eight articles were selected. Out of these eight articles, there were two non-randomized clinical trial studies (25%), one randomized, single-blinded comparative study (12.5%), one retrospective clinical observational study (12.5%) and four randomized clinical trial studies (50%). We employed EndNote X8 and Google Sheets to conduct article reviews and extract relevant data. Following the review phase, the studies underwent analysis and categorization. In all eight reviewed studies, the effectiveness of regenerative medicine in treating hypertrophic scars and keloids has been proven. Out of these studies, five (62.5%) focused on the effectiveness of platelet-rich plasma, two study (25%) examined the effectiveness of stromal vascular fraction and one study (12.5%) explored the efficacy of stem cell-conditioned medium. In two studies (25%), the treatment methods were added to standard treatment, while in six studies (75%), regenerative medicine was used as the sole treatment method and compared with standard treatment. The use of these treatment methods did not result in any serious side effects for the patients. Regenerative medicine is an effective method with minimal side effects for the treatment of hypertrophic scars and keloids. It can be used as a monotherapy or in combination with other treatment methods. However, further studies are needed to thoroughly evaluate the effectiveness of all sub-branches of this method.

The Combination of Mechanically Isolated Stromal Vascular Fraction and Fibrin Hydrogel: A Processing Protocol.

The regenerative potential of adipose-derived stromal cells (ASCs) has gained significant attention in regenerative and translational research. In the past, the extraction of these cells from adipose tissue required a multistep enzyme-based process, resulting in a heterogenous cell mix consisting of ACSs and other cells, which are jointly termed the stromal vascular fraction (SVF). More recently introduced mechanical SVF (mSVF) isolation protocols are less time-consuming and bypass regulatory concerns. We recently proposed a protocol that generates mSVF rich in stromal cells based on a combination of emulsification and centrifugation. One current issue in mSVF application for wound therapy application is the lack of a scaffold providing protection from mechanical manipulation and desiccation. Fibrin hydrogels have been shown to be a useful adjunct in cell transfer for wound healing purposes in the past. In the work herein, we delineate the preparation steps of an mSVF-fibrin hydrogel construct as a novel approach for translational research and clinical application.

Stromal Vascular Fraction Therapy for Knee Osteoarthritis: A Systematic Review.

Background and Objectives: Knee osteoarthritis (OA) is a widespread joint disease, set to increase due to aging and rising obesity. Beyond cartilage degeneration, OA involves the entire joint, including the synovial fluid, bones, and surrounding muscles. Existing treatments, such as NSAIDs and corticosteroid injections, mainly alleviate symptoms but can have complications. Joint replacement surgeries are definitive but carry surgical risks and are not suitable for all. Stromal vascular fraction (SVF) therapy is a regenerative approach using cells from a patient's adipose tissue. SVF addresses as degenerative and inflammatory aspects, with potential for cartilage formation and tissue regeneration. Unlike traditional treatments, SVF may reverse OA changes. Being autologous, it reduces immunogenic risks. Materials and Methods: A systematic search was undertaken across PubMed, Medline, and Scopus for relevant studies published from 2017 to 2023. Keywords included "SVF", "Knee Osteoarthritis", and "Regenerative Medicine". Results: This systematic search yielded a total of 172 articles. After the removal of duplicates and an initial title and abstract screening, 94 full-text articles were assessed for eligibility. Of these, 22 studies met the inclusion criteria and were subsequently included in this review. Conclusions: This review of SVF therapy for knee OA suggests its potential therapeutic benefits. Most studies confirmed its safety and efficacy, and showed improved clinical outcomes and minimal adverse events. However, differences in study designs and sizes require a careful interpretation of the results. While evidence supports SVF's positive effects, understanding methodological limitations is key. Incorporating SVF is promising, but the approach should prioritize patient safety and rigorous research.

Systemically delivered adipose stromal vascular fraction mitigates radiation-induced gastrointestinal syndrome by immunomodulating the inflammatory response through a CD11b+ cell-dependent mechanism.

BACKGROUND: Stromal vascular fraction (SVF) treatment promoted the regeneration of the intestinal epithelium, limiting lethality in a mouse model of radiation-induced gastrointestinal syndrome (GIS). The SVF has a heterogeneous cell composition; the effects between SVF and the host intestinal immunity are still unknown. The specific role of the different cells contained in the SVF needs to be clarified. Monocytes-macrophages have a crucial role in repair and monocyte recruitment and activation are orchestrated by the chemokine receptors CX3CR1 and CCR2. METHODS: Mice exposed to abdominal radiation (18 Gy) received a single intravenous injection of SVF (2.5 × 106 cells), obtained by enzymatic digestion of inguinal fat tissue, on the day of irradiation. Intestinal immunity and regeneration were evaluated by flow cytometry, RT-PCR and histological analyses. RESULTS: Using flow cytometry, we showed that SVF treatment modulated intestinal monocyte differentiation at 7 days post-irradiation by very early increasing the CD11b+Ly6C+CCR2+ population in the intestine ileal mucosa and accelerating the phenotype modification to acquire CX3CR1 in order to finally restore the F4/80+CX3CR1+ macrophage population. In CX3CR1-depleted mice, SVF treatment fails to mature the Ly6C-MCHII+CX3CR1+ population, leading to a macrophage population deficit associated with proinflammatory environment maintenance and defective intestinal repair; this impaired SVF efficiency on survival. Consistent with a CD11b+ being involved in SVF-induced intestinal repair, we showed that SVF-depleted CD11b+ treatment impaired F4/80+CX3CR1+macrophage pool restoration and caused loss of anti-inflammatory properties, abrogating stem cell compartment repair and survival. CONCLUSIONS: These data showed that SVF treatment mitigates the GIS-involving immunomodulatory effect. Cooperation between the monocyte in SVF and the host monocyte defining the therapeutic properties of the SVF is necessary to guarantee the effective action of the SVF on the GIS.

Treatment with stromal vascular fraction of Peyronie's disease - a study protocol.

INTRODUCTION: Peyronie´s disease is the result of an acquired fibrotic plaque in the tunica albuginea. It remains unknown why the condition appears, but it seems to affect up to 9% of all men. It can result in a debilitating curvature of the erect penis, which has extensive impact on the quality of life for many men. Thus, the disease may result in low self-esteem, depression and impaired sexual performance. METHODS: This is a prospective pilot study investigating the feasibility and safety of stromal vascular fraction injection into the plaque of 22 men with Peyronie´s disease in the chronic phase. The stromal vascular fraction is obtained from a small liposuction of 250 ml fat in general anaesthesia and injected the same day. CONCLUSION: We hope to show that injection of stromal vascular fraction is safe and effective in reducing curvature in men with Peyronie´s disease. FUNDING: The study was made possible with funding from: the Region of Southern Denmark, Louis-Hansen Fund, Lizzi and Mogens Staal Fund, Karola Jørgensen Fund, Marie and Børge Kroghs Fund, the Senior Doctors Research Fund OUH, the Fund for gentle Surgery OUH and the PhD fund of the executive board of the South West Denmark Hospital. The funding sources had no influence on the trial design, data collection, analysis or publication. CLINICALTRIALS: gov NCT04771442, EudraCT 2020-004297-22, Danish Medicines Agency 2020090057, National Ethics Committee 74705 and Danish Data Protection Agency (record no. 1/21757).

Adipose-derived stromal vascular fraction (SVF) for the treatment of androgenic alopecia (AGA): a systematic review.

BACKGROUND AND AIM: Androgenetic alopecia (AGA) is a common chronic, hereditary, cutaneous and androgen-dependent condition. Low self-esteem and negatively impact quality of life are often consequences of AGA. Clinical treatment of AGA using SVF (Stromal vascular fraction) has been effective. In fact, hair follicle is affected by various environment factors and one of the most important factors is the vascularity of the scalp which is itself affected bySVF. METHODS: During October 2022 we carried out a systematic review to identify all scientific publications discussing about hair loss treatment with stromal vascular fraction or adipose stem cell. We selected 140 articles. After screening process, we kept 9 articles complying with inclusion criteria.  Results: No serious adverse events were reported in all studies. Despite standardized protocol was not found, all studies reported a statistically significant increase in the number (density) of hair after SVF treatment. Two studies found a significant improvement at pull test. An increase of hair diameter was noticed after treatment. The combination between medical therapy and SVF proved to be advantageous. CONCLUSIONS: SVF is nowadays at the center of studies in the field of regenerative medicine due to its potential applications in many branches of medicine and surgery. The initial results are very promising but furthermore studies are necessary to establish a methodical and systematic research capable of demonstrating its real benefits and the creation of homogenous treatment protocols.

Paracrine signalling between keratinocytes and SVF cells results in a new secreted cytokine profile during wound closure.

Stromal vascular fraction (SVF) cells, and the adipose-derived mesenchymal stem cells they contain, have shown enhanced wound healing in vitro and in vivo, yet their clinical application has been limited. In this regard, understanding the mechanisms that govern SVF-enhanced wound healing would improve their application in the clinic. Here, we show that the SVF cells and keratinocytes engage in a paracrine crosstalk during wound closure, which results in a new cytokine profile that is distinct from the cytokines regularly secreted by either cell type on their own. We identify 11 cytokines, 5 of which are not regularly secreted by the SVF cells, whose expressions are significantly increased during wound closure by the keratinocytes. This new cytokine profile could be used to accelerate wound closure and initiate re-epithelialization without the need to obtain the SVF cells from the patient.