Adipose-derived stromal vascular fraction cells to treat long-term pulmonary sequelae of coronavirus disease 2019: 12-month follow-up.

BACKGROUND AIMS: Long coronavirus disease (COVID) is estimated to occur in up to 20% of patients with coronavirus disease 2019 (COVID-19) infections, with many having persistent pulmonary symptoms. Mesenchymal stromal cells (MSCs) have been shown to have powerful immunomodulatory and anti-fibrotic properties. Autologous adipose-derived (AD) stromal vascular fraction (SVF) contains MSC and other healing cell components and can be obtained by small-volume lipoaspiration and administered on the same day. This study was designed to study the safety of AD SVF infused intravenously to treat the pulmonary symptoms of long COVID. METHODS: Five subjects with persistent cough and dyspnea after hospitalization and subsequent discharge for COVID-19 pneumonia were treated with 40 million intravenous autologous AD SVF cells and followed for 12 months, to include with pulmonary function tests and computed tomography scans of the lung. RESULTS: SVF infusion was safe, with no significant adverse events related to the infusion out to 12 months. Four subjects had improvements in pulmonary symptoms, pulmonary function tests, and computed tomography scans, with some improvement noted as soon as 1 month after SVF treatment. CONCLUSIONS: It is not possible to distinguish between naturally occurring improvement or improvement caused by SVF treatment in this small, uncontrolled study. However, the results support further study of autologous AD SVF as a treatment for long COVID.

Single-Cell RNA Sequencing of Coronary Perivascular Adipose Tissue From End-Stage Heart Failure Patients Identifies SPP1+ Macrophage Subpopulation as a Target for Alleviating Fibrosis.

BACKGROUND: Perivascular adipose tissue (PVAT) is vital for vascular homeostasis, and PVAT dysfunction is associated with increased atherosclerotic plaque burden. But the mechanisms underlining coronary PVAT dysfunction in coronary atherosclerosis remain elusive. METHODS: We performed single-cell RNA sequencing of the stromal vascular fraction of coronary PVAT from 3 groups of heart transplant recipients with end-stage heart failure, including 3 patients with nonobstructive coronary atherosclerosis, 3 patients with obstructive coronary artery atherosclerosis, and 4 nonatherosclerosis control subjects. Bioinformatics was used to annotate the cellular populations, depict the cellular developmental trajectories and interactions, and explore the differences among 3 groups of coronary PVAT at the cellular and molecular levels. Pathological staining, quantitative real-time polymerase chain reaction, and in vitro studies were performed to validate the key findings. RESULTS: Ten cell types were identified among 67 936 cells from human coronary PVAT. Several cellular subpopulations, including SPP1+ (secreted phosphoprotein 1) macrophages and profibrotic fibroadipogenic progenitor cells, were accumulated in PVAT surrounding atherosclerotic coronary arteries compared with nonatherosclerosis coronary arteries. The fibrosis percentage was increased in PVAT surrounding atherosclerotic coronary arteries, and it was positively associated with the grade of coronary artery stenosis. Cellular interaction analysis suggested OPN (osteopontin) secreted by SPP1+ macrophages interacted with CD44 (cluster of differentiation 44)/integrin on fibroadipogenic progenitor cells. Strikingly, correlation analyses uncovered that higher level of SPP1 in PVAT correlates with a more severe fibrosis degree and a higher coronary stenosis grade. In vitro studies showed that conditioned medium from atherosclerotic coronary PVAT promoted the migration and proliferation of fibroadipogenic progenitor cells, while such effect was prevented by blocking CD44 or integrin. CONCLUSIONS: SPP1+ macrophages accumulated in the PVAT surrounding atherosclerotic coronary arteries, and they promoted the migration and proliferation of fibroadipogenic progenitor cells via OPN-CD44/integrin interaction and thus aggravated the fibrosis of coronary PVAT, which was positively correlated to the coronary stenosis burden. Therefore, SPP1+ macrophages in coronary PVAT may participate in the progression of coronary atherosclerosis.

Efficacy of stromal vascular fraction in the treatment of scars: A systematic review and meta-analysis.

OBJECTIVE: Our aim was to assess the effectiveness of stromal vascular fraction (SVF) in treating scars using the latest meta-analysis. METHODS: We used PubMed, Embase, Cochrane, and Web of Science to search the studies used to evaluate the efficacy of SVF in scar treatment. At least one of the following outcome measures were reported: vascularity, pigmentation, thickness, relief, pliability, surface area, pain, itching and color. RESULTS: A total of four eligible articles comprising 145 patients (64 SVF patients and 81 non-SVF patients) were included. The findings of this meta-analysis indicated that SVF had significant therapeutic effects in terms of vascularity (SMD/MD, 95% CI: -1.12, -0.02; p = 0.04), itching (SMD/MD, 95% CI: -0.61, -0.13; p = 0.002), POSAS (SMD/MD, 95% CI: -5.93, -1.47; p = 0.001), and thickness (SMD/MD, 95% CI: -1.04, -0.35; p < 0.001). In terms of OSAS (SMD/MD, 95% CI: -9.14, 0.59; p = 0.09), pigmentation (SMD/MD, 95% CI: -1.02, 0.06; p = 0.08), relief (SMD/MD, 95% CI: -1.14, 0.16; p = 0.14), surface area (SMD/MD, 95% CI: -0.91, 0.26; p = 0.27), PSAS (SMD/MD, 95% CI: -7.20, 0.49; p = 0.09), pain (SMD/MD, 95% CI: -0.87, 0.07; p = 0.10), pliability (SMD/MD, 95% CI: -0.57, 0.01; p = 0.06), and color (SMD/MD, 95% CI: -1.78, 0.48; p = 0.26), there were no significant statistical differences. CONCLUSION: In view of the heterogeneity and potential selective bias, further large-scale, prospective, and multicenter clinical trials are needed to confirm the efficacy and reliability of SVF in the treatment of scars.

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 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.

The investigation and comparison of the efficacy and safety of stromal vascular fraction (SVF), platelet rich plasma (PRP), and 1064-nm Q-switched Nd:YAG laser in reducing nanofat treated infraorbital dark circles and wrinkles: A controlled blinded randomized clinical trial.

BACKGROUND: To evaluate the efficacy and safety of stromal vascular fraction (SVF), platelet rich plasma (PRP), and 1064-nm Q-switched Nd:YAG laser in reducing nanofat treated dark circles and wrinkles under the eyes. METHOD: This study was a single-blinded randomized clinical trial conducted on patients with suborbital darkening under the eyes that randomly divided into control and case groups. In the control group, 15 patients were treated with one session of nanofat injection only, and five patients of each intervention groups received one session of nanofat+SVF injection, nanofat+PRP injection, and nanofat injection+Nd:YAG laser, respectively. Assessments methods were (1) evaluation of the degree of darkness and repair under the eyes by a blinded dermatologist based on clinical photographs, (2) investigating patient satisfaction, (3) using biometric variables for color, thickness, and density of the skin (only 3 months after the treatment), and (4) recording the possible adverse effects. CONCLUSION: In terms of the extent of reduction in the intensity of darkness under the eyes, the combined treatment of nanofat injection together with SVF, PRP, and Nd:YAG laser had a much greater therapeutic effect than nanofat injection alone. In all three groups of combined treatments, patients were 100% satisfied. In terms of biometric variables, amount of changes in colorimeter, complete and dermal thickness, complete and dermal density, between the different groups was statistically significant. The use of combined treatments including nanofat with SVF injection, PRP, and 1064 Q-switched Nd:YAG laser may be more effective than nanofat alone, in reducing infraorbital dark circles and wrinkles.

Multiple intra-articular injections of autologous stromal vascular fractions for the treatment of multicompartmental osteoarthritis in both the tibiofemoral and patellofemoral joint: a single-blind randomized controlled study.

BACKGROUND: Multicompartmental osteoarthritis (MOA) in both tibiofemoral and patellofemoral joints is a more commonly occurring, but neglected, clinical condition, and we examined the short-term safety and efficacy of autologous stromal vascular fractions (SVFs) for MOA using a single-blind, prospective, randomized, placebo-controlled trial. METHODS: Seventy MOA patients were recruited and randomly assigned to the SVF group and hyaluronic acid (HA) group (control group). The scores of visual analog scale, the Western Ontario and McMaster University Osteoarthritis Index, and the Samsung Medical Center patellofemoral scoring system were assessed and compared between the two groups 3, 6 and 12 months after treatment. RESULTS: The SVF group had significantly better visual analog scale scores than the HA group at 6 and 12 months after treatment and had better Western Ontario and McMaster University Osteoarthritis Index scores than the HA group only at 6 months after treatment. For Samsung Medical Center patellofemoral scoring system of the patellofemoral joint, the SVF group had significantly better scores than the control group at all postoperative time points. The proportion of patients whose visual analog scale and Western Ontario and McMaster University Osteoarthritis Index scores were above the minimal clinically important improvement was higher in the SVF group than in the HA group in the majority of assessments. The improvement of bone marrow by SVF treatment was significantly better than that of the HA group as observed by pre- and postoperative Magnetic resonance imaging (MRI). CONCLUSIONS: Multiple intra-articular injection of autologous SVF reduces pain and improves function in the short term in patients with early or midstage MOA. However, there was heterogeneity in the improvement of overall knee and isolated patellofemoral joint after treatment.

Beneficial effects of adipose-derived stromal vascular fraction on testicular injury caused by busulfan.

The use of stem cells can attenuate testicular injury and promote sperm production. The adipose-derived stromal vascular fraction (SVF) has become an attractive cell source for cell-based therapies. In this study, we aimed to investigate the therapeutic efficacy of SVF on busulfan-induced testicular damage in rats. Twenty-four male rats were randomly divided into control, busulfan, SVF, and busulfan + SVF groups. Testicular damage was induced by intraperitoneal administration of busulfan (35 mg/kg). SVF obtained from human adipose tissue using Lipocube SVF™ was injected into rats 5 weeks after busulfan administration. At the end of the 8th week, rats were sacrificed, and histopathological, biochemical, and western blotting analyses were performed. No harmful effects of SVF on healthy testis tissue and sperm parameters were detected. SVF improved busulfan-induced oxidative stress in both testis tissue and serum. SVF injection to damaged testicular tissue resulted in increases in the healthy spermatozoon numbers and decreases in the abnormal tail numbers. Additionally, SVF increased bax/Bcl, DAZL, and TGF-ß1 levels whereas decreased ATG5 and NF-kB levels. According to the results we obtained in this study, we suggest that SVF is beneficial in restoring damaged tissue by primarily being a multipotent cell source, by inhibiting oxidative stress and converting necrotic cell death to apoptotic cell death. In the future, clinical applications should bring higher benefits. Since SVF is the patient's own tissue, being harmless, it will offer an advantageous supportive treatment option for patients already weakened by cancer and anticancer therapy.

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 .

Mechanical Purification of Lipofilling: The Relationship Between Cell Yield, Cell Growth, and Fat Volume Maintenance.

BACKGROUND: The mechanical manipulations of fat tissue represented from centrifugation, filtration, washing, and fragmentation were considered the most effective strategies aiming to obtain purified lipofilling with different impacts both in terms of adipose-derived stem cells amount contained in stromal vascular fraction, and fat volume maintenance. OBJECTIVES: The present work aimed to report results in fat volume maintenance obtained by lipofilling purification based on the combined use of washing and filtration, in a clinical study, and to deeply investigate the adipose-derived stem cells yield and growth capacity of the different stromal vascular fraction extraction techniques with an in vitro approach. METHODS: A preliminary prospective, case-control study was conducted. 20 patients affected by face and breast soft tissue defects were treated with lipofilling and divided into two groups: n = 10 patients (study group) were treated with lipofilling obtained by washing and filtration procedures, while n = 10 (control group) were treated with lipofilling obtained by centrifugation according to the Coleman technique. 6 months after the lipofilling, the volume maintenance percentage was analyzed by clinical picture and magnetic resonance imaging comparisons. Additionally, extracted stromal vascular fraction cells were also in vitro analyzed in terms of adipose-derived stem cell yield and growth capacity. RESULTS: A 69% ± 5.0% maintenance of fat volume after 6 months was observed in the study group, compared with 44% ± 5.5% in the control group. Moreover, the cellular yield of the control group resulted in 267,000 ± 94,107 adipose-derived stem cells/mL, while the study group resulted in 528,895 ± 115,853 adipose-derived stem cells /mL, with a p-value = 0.1805. Interestingly, the study group showed a fold increase in cell growth of 6758 ± 0.7122, while the control group resulted in 3888 ± 0.3078, with a p < 0.05 (p = 0.0122). CONCLUSIONS: The comparison of both groups indicated that washing and filtration were a better efficient system in lipofilling preparation, compared to centrifugation, both in terms of volume maintenance and adipose-derived stem cell growth ability. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://www.springer.com/00266 .

Isolation of the Stromal Vascular Fraction Using a New Protocol with All Clinical-Grade Drugs: From Basic Study to Clinical Application.

OBJECTIVE: The purpose of this study was to evaluate the yield, viability, clinical safety, and efficacy of the stromal vascular fraction (SVF) separated with a new protocol with all clinical-grade drugs. MATERIALS AND METHODS: SVF cells were isolated from lipoaspirate obtained from 13 participants aged from 30 to 56 years by using a new clinical protocol and the laboratory protocol. The cell yield, viability, morphology, mesenchymal stem cell (MSC) surface marker expression, and differentiation abilities of the SVF cells harvested from the two protocols were compared. Furthermore, three related clinical trials were conducted to verify the safety and efficiency of SVF cells isolated by the new clinical protocol. RESULTS: There were no significant differences in the yield, viability, morphology, and differentiation potential of the SVFs isolated with the clinical protocol and laboratory protocol. Adipose-derived mesenchymal stem cell (ASC) surface marker expression, including that of CD14, CD31, CD44, CD90, CD105, and CD133, was consistent between the two protocols. Clinical trials have demonstrated the effectiveness of the SVF isolated with the new clinical protocol in improving skin grafting, promoting mechanical stretch-induced skin regeneration and improving facial skin texture. No complications occurred. CONCLUSION: SVF isolated by the new clinical protocol had a noninferior yield and viability to that of the SVF separated by the laboratory protocol. SVFs obtained by the new protocol can be safely and effectively applied to improve skin grafting, promote mechanical stretch-induced skin regeneration, and improve facial skin texture. TRIAL REGISTRATION: The trials were registered with the ClinicalTrials.gov (NCT03189628), the Chinese Clinical Trial Registry (ChiCTR2000039317), and the ClinicalTrials.gov (NCT02546882). All the three trials were not patient-funded trials. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Pilot Study for Isolation of Stromal Vascular Fraction with Collagenase Using an Automated Processing System.

There are many potential therapeutic applications for autologous adipose-derived stromal cells. These cells are found in a heterogeneous population isolated from adipose tissue called the stromal vascular fraction (SVF). Closed automated systems are available to release cells from the adherent stroma. Here, we test one system to evaluate the heterogeneous output for yield, purity, cellular characterization, and stemness criteria. The SVF was isolated from three donors using the Automated Cell Station (ACS) from BSL Co., Ltd., Busan, Republic of Korea. The SVF cellular output was characterized for cell yield and viability, immunophenotyping analysis, pluripotent differentiation potential, adhesion to plastic, and colony-forming units. Additionally, the SVF was tested for endotoxin and collagenase residuals. The SVF yield from the ACS system was an average volume of 7.9 ± 0.5 mL containing an average of 19 × 106 nucleated cells with 85 ± 12% viability. Flow cytometry identified a variety of cells, including ASCs (23%), macrophages (24%), endothelial cells (5%), pericytes (4%), and transitional cells (0.5%). The final concentrated product contained cells capable of differentiating into adipogenic, chondrogenic, and osteogenic phenotypes. Furthermore, tests for SVF sterility and purity showed no evidence of endotoxin or collagenase residuals. The ACS system can efficiently process cells from adipose tissue within the timeframe of a single surgical procedure. The cellular characterization indicated that this system can yield a sterile and concentrated SVF output, providing a valuable source of ASCs within the heterogeneous cell population.

The role of orthobiologics in chronic wound healing.

Chronic wounds, characterized by prolonged healing processes, pose a significant medical challenge with multifaceted aetiologies, including local and systemic factors. Here, it explores the complex pathogenesis of chronic wounds, emphasizing the disruption in the normal phases of wound healing, particularly the inflammatory phase, leading to an imbalance in extracellular matrix (ECM) dynamics and persistent inflammation. Senescent cell populations further contribute to impaired wound healing in chronic lesions. Traditional medical management focuses on addressing underlying causes, but many chronic wounds resist to conventional treatments, necessitating innovative approaches. Recent attention has turned to autologous orthobiologics, such as platelet-rich plasma (PRP), platelet-rich fibrin (PRF) and mesenchymal stem cells (MSCs), as potential regenerative interventions. These biologically derived materials, including bone marrow aspirate/concentrate (BMA/BMAC) and adipose tissue-derived stem cells (ADSCs), exhibit promising cytokine content and regenerative potential. MSCs, in particular, have emerged as key players in wound healing, influencing inflammation and promoting tissue regeneration. This paper reviews relevant scientific literature regarding basic science and brings real-world evidence regarding the use of orthobiologics in the treatment of chronic wounds, irrespective of aetiology. The discussion highlights the regenerative properties of PRP, PRF, BMA, BMAC and SVF, showcasing their potential to enhance wound healing. Despite advancements, further research is essential to elucidate the specific roles of each orthobiologic and determine optimal applications for different wound types. The conclusion underscores the evolving landscape in chronic wound management, with a call for more comprehensive studies to refine treatment strategies and maximize the benefits of regenerative medicine.

Analyzing the Clinical Potential of Stromal Vascular Fraction: A Comprehensive Literature Review.

Background: Regenerative medicine is evolving with discoveries like the stromal vascular fraction (SVF), a diverse cell group from adipose tissue with therapeutic promise. Originating from fat cell metabolism studies in the 1960s, SVF's versatility was recognized after demonstrating multipotency. Comprising of cells like pericytes, smooth muscle cells, and, notably, adipose-derived stem cells (ADSCs), SVF offers tissue regeneration and repair through the differentiation and secretion of growth factors. Its therapeutic efficacy is due to these cells' synergistic action, prompting extensive research. Methods: This review analyzed the relevant literature on SVF, covering its composition, action mechanisms, clinical applications, and future directions. An extensive literature search from January 2018 to June 2023 was conducted across databases like PubMed, Embase, etc., using specific keywords. Results: The systematic literature search yielded a total of 473 articles. Sixteen articles met the inclusion criteria and were included in the review. This rigorous methodology provides a framework for a thorough and systematic analysis of the existing literature on SVF, offering robust insights into the potential of this important cell population in regenerative medicine. Conclusions: Our review reveals the potential of SVF, a heterogeneous cell mixture, as a powerful tool in regenerative medicine. SVF has demonstrated therapeutic efficacy and safety across disciplines, improving pain, tissue regeneration, graft survival, and wound healing while exhibiting immunomodulatory and anti-inflammatory properties.

Recent Trends in Adipose Tissue-Derived Injectable Therapies for Osteoarthritis: A Scoping Review of Animal Models.

Background and Objectives: This scoping review investigates recent trends in adipose tissue-derived injectable therapies for osteoarthritis (OA) in animal models, focusing on minimally manipulated or lightly processed adipose tissue. By evaluating and examining the specific context in which these therapies were investigated across diverse animal OA models, this review aims to provide valuable insights that will inform and guide future research and clinical applications in the ongoing pursuit of effective treatments for osteoarthritis. Materials and Methods: This research conducted a comprehensive literature review of PubMed and Embase to determine studies about minimally manipulated adipose tissue-derived injectable therapies for osteoarthritis investigated using animal models. The primary search found 530 results. After excluding articles that focused on spontaneous osteoarthritis; on transfected, preconditioned, cultured, or co-cultured adipose-derived stem cells; and articles with unavailable full text, we included 11 articles in our review. Results: The examined therapies encompassed mechanical micro-fragmented adipose tissue (MFAT) and stromal vascular fraction (SVF) obtained via collagenase digestion and centrifugation. These interventions were evaluated across various animal models, including mice, rats, rabbits, and sheep with induced OA. Notably, more studies concentrated on surgically induced OA rather than chemically induced OA. The assessment of these therapies focused on elucidating their protective immunomodulatory, anti-inflammatory, and chondroregenerative potential through comprehensive evaluations, including macroscopic assessments, histological analyses, immunohistochemical examinations, and biochemical assays. Conclusions: This review provides a comprehensive analysis of adipose tissue-derived injectable therapies for osteoarthritis across diverse animal models. While revealing potential benefits and insights, the heterogeneity of data and the limited number of studies highlight the need for further research to formulate conclusive recommendations for clinical applications.

[Closing of nasal septum perforation using adipose stromal vascular fraction: an experimental study]. / Zakrytie perforatsii peregorodki nosa s primeneniem stromal'no-vaskulyarnoi zhirovoi fraktsii: eksperimental'noe issledovanie.

Nasal septal perforation (NSP) is a complex problem in otorhinolaryngology, which leads to impaired nasal breathing and dryness in the nose. This reduces the patient's quality of life and leads to psychological discomfort. The treatment of nasal septum perforation is selected taking into account the clinical manifestations, perforation parameters and general condition of the patient. Currently, a large number of different surgical methods have been described in order to closing the defect of nasal septum. To date, there is no universally accepted method for closing NSP, which stimulates the search and development of new treatment options. OBJECTIVE: Under experimental conditions, to study a new method for closing nasal septum perforation using a collagen scaffold together with adipose stromal vascular fraction containing multipotent mesenchymal stromal cells. MATERIAL AND METHODS: The experiment was carried out on a model of nasal septum perforation in 24 male rabbits divided into four groups, depending on the construct, implanted into the defect zone: the 1st group was the control group - without the introduction of implantation material; the 2nd group - collagen scaffold without adipose stromal vascular fraction; the 3rd group - collagen scaffold with xenogenic adipose stromal vascular fraction; the 4th group - collagen scaffold with allogeneic adipose stromal vascular fraction with further dynamic evaluation of endoscopic control on day 14, after 1 month, 3 months, and 6 months. At month 6, the animals were removed from the experiment, followed by morphological examination in color with hematoxylin and eosin, as well as safranin and methyl green. RESULTS: As a result of the experiment using adipose stromal vascular fraction of allogeneic and xenogenic origin, closing of perforation of the nasal septum of a rabbit for 3 months of dynamic endoscopic control, as well as according to morphological research, was demonstrated. CONCLUSION: Our study showed that the use of adipose stromal vascular fraction containing not only endothelial cells and pericytes, but also multipotent mesenchymal stromal cells in combination with a collagen scaffold closes the perforation of the nasal septum in a rabbit, without increasing the risk of violations of habitual vital activity.

Stromal Vascular Fraction Obtained From Subcutaneous Adipose Tissue: Ex-Obese and Older Population as Main Clinical Targets.

INTRODUCTION: Human adipose tissue contains a heterogeneous and synergistic mixture of cells called stromal vascular fraction (SVF) with highly proliferative and angiogenic properties, conferring promising applicability in the field of regenerative medicine. This study aims to investigate if age, body mass index (BMI), history of obesity and massive weight loss, and harvest site are related to SVF cell marker expression. METHODS: A total of 26 samples of subcutaneous adipose tissue were harvested from patients admitted to the Plastic and Reconstructive department in University Hospital Center of São João, Porto, Portugal, for body contouring surgery. The percentage of cells expressing CD31, CD34, CD45, CD73, CD90, and CD105 was assessed and compared with patient's age, BMI, history of obesity and massive weight loss (ex-obese group), and harvest site. RESULTS: In the ex-obese group, a significantly higher number of cells expressing CD90 (P = 0.002) was found. BMI, harvest site, and age appear to have no association with SVF subpopulations. CONCLUSIONS: This study suggests that ex-obese patients have a higher percentage of SVF cells expressing CD90, which correlates with higher proliferative and angiogenic rates. The effect of former obesity and massive weight loss on the expression of CD90 is a new and relevant finding because it makes this population a suitable candidate for reconstructive and aesthetic surgery and other fields of regenerative medicine. The use of SVF appears also promising in older patients because no negative correlation between increasing age and different cell markers expression was found.

Adipose Derived Stromal Vascular Fraction and Mesenchymal Stem Cells Improve Angiogenesis in a Rat Hindlimb Ischaemia Model.

OBJECTIVE: This study aimed to investigate the effect of human adipose tissue derived stromal vascular fraction (AD-SVF) and mesenchymal stem cells (AD-MSCs) on blood flow recovery and neovascularisation in a rat hindlimb ischaemia model. METHODS: SVF was isolated using an automated centrifugal system, and AD-MSCs were obtained from adherent cultures of SVF cells. Rats were divided into four groups of six rats each: non-ischaemia (Group 1); saline treated ischaemia (Group 2); SVF treated ischaemia (Group 3); and AD-MSC treated ischaemia (Group 4). Unilateral hindlimb ischaemia was induced in Sprague-Dawley rats via femoral artery ligation. Saline, SVF, or AD-MSCs were injected intramuscularly into the adductor muscle intra-operatively. Cell viability was calculated as the percentage of live cells relative to total cell number. Blood flow improvement, muscle fibre injury, and angiogenic properties were validated using thermal imaging and histological assessment. RESULTS: The viabilities of SVF and AD-MSCs were 83.3% and 96.7%, respectively. Group 1 exhibited no significant temperature difference between hindlimbs, indicating a lack of blood flow changes. The temperature gradient gradually decreased in SVF and AD-MSC treated rats compared with saline treated rats. In addition, only normal muscle fibres with peripherally located nuclei were observed in Group 1. Groups 3 and 4 exhibited significantly fewer centrally located nuclei, indicating less muscle damage compared with Group 2. Regarding angiogenic properties, CD31 staining of endothelial cells showed similar patterns among all groups, whereas expression of vascular endothelial growth factor, as a crucial angiogenesis factor, was enhanced in the SVF and AD-MSC treated groups. CONCLUSION: SVF and AD-MSCs improved blood flow and neovascularisation in a rat hindlimb ischaemia model, suggesting their potential ability to promote angiogenesis. Further extensive research is warranted to explore their potential applications in the treatment of severe lower extremity arterial disease.

SVF-GEL Cryopreserved for Different Times Exhibits Varied Preservation and Regeneration Potential After Transplantation in a Mouse Model.

BACKGROUND: Matrix vascular component (SVF) gels derived from fat preserve tissue integrity and cell viability under cryopreserved conditions, making them easy to inject again for later use. Here, we compared the preservation power and regeneration potential of SVF-gel under different cryopreservation times. METHODS: The SVF-gel stored under - 20 °C, without cryoprotectant cryopreservation for 5, 15, and 45 days, with fresh SVF-gel as control. We evaluated the rate of volume retention after thawing the SVF-gel and the apoptosis rate of adipose-derived stem cells. Next, we analyzed retention rated, adipogenesis, angiogenesis, and connective tissue hyperplasia of the grafts, one month after subcutaneously transplanting the specimen into immunodeficient mice. RESULTS: SVF-gel cryopreserved for 5 and 15 days exhibited no significant different in apoptosis rates relative to the control group. Extending the cryopreservation time to 45 days resulted in significantly increased and decreased apoptosis and volume retention rates of SVF-gel, respectively. SVF-gel grafts cryopreserved for 5 and 15 days exhibited no significant differences from those in the control group, although their weights and volumes still fluctuated. Extending the cryopreservation time to 45 days resulted in significantly decreased retention rates of the grafts. Histologically, extending freezing time resulted in a gradual decline in the graft's health adipose tissue, as well as decreased angiogenesis, and connective tissue hyperplasia. CONCLUSION: Simple freezing of SVF-gel at - 20 °C conferred them with sufficient cell viability. Notably, short-term cryopreservation did not significantly increase the apoptosis rate, and it still had a certain regeneration after transplantation. However, prolonging freezing time to 45 days resulted in increased apoptosis rate and worsened transplantation effect. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

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

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