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Abstract Background Vasculopathy underlies diabetic complications, with perivascular adipose tissue (PVAT) playing crucial roles in its development. However, the changes in the cellular composition and function of PVAT, including the specific cell subsets and mechanisms implicated in type 2 diabetes mellitus (T2DM) vasculopathy, remain unclear. Methods To address the above issues, we performed single-cell RNA sequencing on the stromal vascular fraction (SVF) of PVAT from normal and T2DM rats. Then, various bioinformatics tools and functional experiments were used to investigate the characteristic changes in the cellular profile of diabetic PVAT SVF, their implications, and the underlying mechanisms. Results Our study reveals the single-cell landscape of the SVF of PVAT, demonstrating its considerable heterogeneity and significant alterations in T2DM, including an enhanced inflammatory response and elevated proportions of macrophages and natural killer (NK) cells. Moreover, macrophages are critical hubs for cross-talk among various cell populations. Notably, we identified a decreased Pdpn + macrophage subpopulation in the PVAT of T2DM rats and confirmed this in mice and humans. In vitro and in vivo studies demonstrated that Pdpn + macrophages alleviated insulin resistance and modulated adipokine/cytokine expression in adipocytes via the Pla2g2d-DHA/EPA-GPR120 pathway. This subset also enhances the function of vascular endothelial and smooth muscle cells, inhibits vascular inflammation and oxidative stress, and improves vasodilatory function, thereby protecting blood vessels. Conclusion Pdpn + macrophages exhibit significant vascular protective effects by alleviating insulin resistance and modulating adipokine/cytokine expression in PVAT adipocytes. This macrophage subtype may therefore play pivotal roles in mitigating vascular complications in T2DM. Our findings also underscore the critical role of immune-metabolic cross-talk in maintaining tissue homeostasis. Graphical Abstract

Background: Vasculopathy underlies diabetic complications, with perivascular adipose tissue (PVAT) playing crucial roles in its development. However, the changes in the cellular composition and function of PVAT, including the specific cell subsets and mechanisms implicated in type 2 diabetes mellitus (T2DM) vasculopathy, remain unclear. Methods: To address the above issues, we performed single-cell RNA sequencing on the stromal vascular fraction (SVF) of PVAT from normal and T2DM rats. Then, various bioinformatics tools and functional experiments were used to investigate the characteristic changes in the cellular profile of diabetic PVAT SVF, their implications, and the underlying mechanisms. Results: Our study reveals the single-cell landscape of the SVF of PVAT, demonstrating its considerable heterogeneity and significant alterations in T2DM, including an enhanced inflammatory response and elevated proportions of macrophages and natural killer (NK) cells. Moreover, macrophages are critical hubs for cross-talk among various cell populations. Notably, we identified a decreased Pdpn+ macrophage subpopulation in the PVAT of T2DM rats and confirmed this in mice and humans. In vitro and in vivo studies demonstrated that Pdpn+ macrophages alleviated insulin resistance and modulated adipokine/cytokine expression in adipocytes via the Pla2g2d-DHA/EPA-GPR120 pathway. This subset also enhances the function of vascular endothelial and smooth muscle cells, inhibits vascular inflammation and oxidative stress, and improves vasodilatory function, thereby protecting blood vessels. Conclusion: Pdpn+ macrophages exhibit significant vascular protective effects by alleviating insulin resistance and modulating adipokine/cytokine expression in PVAT adipocytes. This macrophage subtype may therefore play pivotal roles in mitigating vascular complications in T2DM. Our findings also underscore the critical role of immune-metabolic cross-talk in maintaining tissue homeostasis. [ABSTRACT FROM AUTHOR]

Sigmoidovaginal fistula (SVF) is an extremely distressing and complex condition that significantly impacts a patient’s quality of life. The successful management of SVF relies on accurately identifying the fistula’s location and tract. However, preoperative localization can be challenging in certain cases. In this report, we describe a rare complication in a patient with stage IVA cervical cancer who developed SVF after concurrent chemoradiotherapy. Conventional diagnostic methods, including electron colonoscopy, methylene blue testing, and fistulography, were unable to locate the fistula. As an alternative, we used a non-contact hysteroscopic technique, which successfully identified the location, size, and number of fistulas. This method is particularly effective for patients with SVF, especially in postmenopausal women with narrowed or adherent vaginal tracts, women with intact hymen, and those with complex, high-grade vaginal fistulas resulting from cancer treatment with chemoradiotherapy.

IntroductionOrthobiologics, such as autologous nanofat, are emerging as a potential treatment option for osteoarthritis (OA), a common degenerative joint causing pain and disability in the elderly. Nanofat, a minimally processed human fat graft rich in stromal vascular fraction (SVF) secretory factors, has shown promise in relieving pain. This study aimed to elucidate the molecular mechanisms underlying nanofat treatment of OA-affected cells and compare two filtration systems used for nanofat preparation.MethodsChondrocytes and synoviocytes were isolated from articular cartilage and synovium of 22 OA-patients. Lipoaspirates from 13 OA-patients were emulsified using the Adinizer® or Lipocube™ Nano filter systems to generate nanofat. The fluid phase of SVF from both filtered and unfiltered lipoaspirates was applied to OA-affected cells. Luminex multiplex ELISA were performed with lipoaspirates and cell supernatants alongside functional assays evaluating cell migration, proliferation, metabolic activity, and senescence.ResultsA total of 62 cytokines, chemokines, growth factors, neuropeptides, matrix-degrading enzymes, and complement components were identified in lipoaspirates. Among these, significant concentration differences were observed for TIMP-2, TGF-ß3, and complement component C3 between the filtered and unfiltered samples. Nanofat enhanced chondrocyte proliferation and migration, as well as synoviocyte migration and metabolic activity, while reducing chondrocyte metabolic activity. Pain-related factors like β-NGF, MCP-1, Substance P, VEGF, and αCGRP were reduced, while anti-inflammatory TGF-β1+3 increased and pro-inflammatory cytokines (IL-5, IL-7, IL-15, and IFN-γ) decreased. Nanofat also elevated secretion of complement components and TIMPs in both cell types. Notably, our results revealed no significant differences in cellular effects between sSVF filtered using the Adinizer® and Lipocube™ Nano systems, as well as compared to unfiltered sSVF.DiscussionHere, we provide first insights into how autologous nanofat therapy may ameliorate OA by enhancing chondrocyte proliferation and synoviocyte migration while modulating inflammatory and pain-related factors. However, further research is needed to determine its effects on cartilage regeneration.

Introduction: Osteoarthritis is a degenerative condition of the cartilage, often common among the population and occurs frequently with aging. Many factors are decisive for the development of its pathogenesis such as age, obesity, trauma, mechanical load, and modification of synovial biology. The main features of osteoarthritis are chondrocytes and cartilage matrix loss, which lead to pain, loss of function of the whole joint, and disability, representing a relevant health problem. Recently, a new therapeutic approach based on cell therapy has been studying the regenerative ability of mesenchymal stem cells for osteoarthritic chondrocytes. Aim: This in vitro study clarifies the regenerative effects of multipotent adipose-derived stem cells and the pluripotent amniotic epithelial stem cells on arthrosis chondrocytes by performing co-culture experiments. Methods: We studied the regenerative potential of secretome (soluble factors and extracellular vesicles), mesenchymal stem cells, and the adipose stromal vascular fraction. The regenerative effects were evaluated by gene and protein expression analysis of articular cartilage-specific genes and proteins like col2a1, acan, and sox9. Results: Mesenchymal stem cells, secretome, and adipose stromal vascular fractions influenced the cartilage genes and protein expression. Conclusions: The results indicate that the treatment with mesenchymal stem cells could be the best biological approach for cartilage regenerative medicine. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background/Objectives: This retrospective observational study sought to determine the efficacy and safety of an innovative combined treatment protocol using guided Superficial Enhanced Fluid Fat Injection (SEFFI) and calcium hydroxylapatite (CaHA) in facial rejuvenation. Methods: A total of 158 patients (149 females and 9 males) underwent the combined treatment of guided SEFFI and diluted/hyperdiluted CaHA. The study evaluated treatment outcomes at 30, 90, and 150 days post-treatment using the Global Aesthetic Improvement Scale (GAIS) and three-dimensional photogrammetric analysis. Results: The combined treatment demonstrated consistent enhancement in skin quality and facial volume across temporal, malar, zygomatic, and jawline regions. At 90 days post-treatment, substantial improvements were observed, with the GAIS scores reflecting significant enhancements in both skin quality and volume, which were sustained or slightly improved by 150 days. Minor complications, predominantly ecchymosis at the injection sites, resolved within a week, confirming the treatments' safety. Conclusions: The integration of guided SEFFI and CaHA resulted in significant improvements in skin quality and facial volume with minimal complications. Further research is recommended to consolidate these findings and explore long-term outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Lichen sclerosus (LS) is a chronic inflammatory dermatosis predominantly affecting the anogenital area, with potential systemic implications. Objective: Our aim is to elucidate its clinical characteristics and management strategies. Methods: We conducted a retrospective observational study on adult patients with LS referred to our center between January 2022 and December 2023. Results: Forty-six adult subjects affected by LS were enrolled in the present study. The majority of patients presented with genital involvement, but a significant subset exhibited extragenital LS and concomitant immune-mediated disorders. Common symptoms included itching, soreness, and dyspareunia, with characteristic skin findings of erythema and atrophy. Topical corticosteroids were the mainstay of therapy, complemented by alternative treatments in refractory cases. Alternative therapeutic approaches, such as platelet rich plasma or adipose-tissue derived stromal/stem cell-based strategies, were effectively employed in refractory cases, in the absence of major adverse events. Conclusions: Our findings underscore the importance of alternative approaches in the management of LS and highlight the need for further research to elucidate its pathogenesis and optimize therapeutic interventions.

The injection of biologic products for musculoskeletal pathologies is an emerging and promising field; however, dubious and unsafe uses for these products are often marketed. The Food and Drug Administration (FDA) has determined the need for varying degrees of regulation for these products for safety and efficacy. These regulations are frequently updated and federally enforced. As the regulatory landscape changes, clinicians using biologic products must stay informed to remain within the purview of the FDA. This article describes the current regulations of the most common products: platelet-rich plasma, bone marrow aspirate concentrate, adipose-derived products, and birth tissue products.

Abstract Aims and objectives The aim of this study is to systematically review randomized controlled clinical trials (RCTs) studying various types of regenerative medicine methods (such as platelet-rich plasma, stromal vascular fraction, cell therapy, conditioned media, etc.) in treating specific dermatologic diseases. Rejuvenation, scarring, wound healing, and other secondary conditions of skin damage were not investigated in this study. Method Major databases, including PubMed, Scopus, and Web of Science, were meticulously searched for RCTs up to January 2024, focusing on regenerative medicine interventions for specific dermatologic disorders (such as androgenetic alopecia, vitiligo, alopecia areata, etc.). Key data extracted encompassed participant characteristics and sample sizes, types of regenerative therapy, treatment efficacy, and adverse events. Results In this systematic review, 64 studies involving a total of 2888 patients were examined. Women constituted 44.8% of the study population, while men made up 55.2% of the participants, with an average age of 27.64 years. The most frequently studied skin diseases were androgenetic alopecia (AGA) (45.3%) and vitiligo (31.2%). The most common regenerative methods investigated for these diseases were PRP and the transplantation of autologous epidermal melanocyte/keratinocyte cells, respectively. Studies reported up to 68.4% improvement in AGA and up to 71% improvement in vitiligo. Other diseases included in the review were alopecia areata, melasma, lichen sclerosus et atrophicus (LSA), inflammatory acne vulgaris, chronic telogen effluvium, erosive oral lichen planus, and dystrophic epidermolysis bullosa. Regenerative medicine was found to be an effective treatment option in all of these studies, along with other methods. The regenerative medicine techniques investigated in this study comprised the transplantation of autologous epidermal melanocyte/keratinocyte cells, isolated melanocyte transplantation, cell transplantation from hair follicle origins, melanocyte–keratinocyte suspension in PRP, conditioned media injection, a combination of PRP and basic fibroblast growth factor, intravenous injection of mesenchymal stem cells, concentrated growth factor, stromal vascular fraction (SVF), a combination of PRP and SVF, and preserving hair grafts in PRP. Conclusion Regenerative medicine holds promise as a treatment for specific dermatologic disorders. To validate our findings, it is recommended to conduct numerous clinical trials focusing on various skin conditions. In our study, we did not explore secondary skin lesions like scars or ulcers. Therefore, assessing the effectiveness of this treatment method for addressing these conditions would necessitate a separate study.

Aims and objectives: The aim of this study is to systematically review randomized controlled clinical trials (RCTs) studying various types of regenerative medicine methods (such as platelet-rich plasma, stromal vascular fraction, cell therapy, conditioned media, etc.) in treating specific dermatologic diseases. Rejuvenation, scarring, wound healing, and other secondary conditions of skin damage were not investigated in this study. Method: Major databases, including PubMed, Scopus, and Web of Science, were meticulously searched for RCTs up to January 2024, focusing on regenerative medicine interventions for specific dermatologic disorders (such as androgenetic alopecia, vitiligo, alopecia areata, etc.). Key data extracted encompassed participant characteristics and sample sizes, types of regenerative therapy, treatment efficacy, and adverse events. Results: In this systematic review, 64 studies involving a total of 2888 patients were examined. Women constituted 44.8% of the study population, while men made up 55.2% of the participants, with an average age of 27.64 years. The most frequently studied skin diseases were androgenetic alopecia (AGA) (45.3%) and vitiligo (31.2%). The most common regenerative methods investigated for these diseases were PRP and the transplantation of autologous epidermal melanocyte/keratinocyte cells, respectively. Studies reported up to 68.4% improvement in AGA and up to 71% improvement in vitiligo. Other diseases included in the review were alopecia areata, melasma, lichen sclerosus et atrophicus (LSA), inflammatory acne vulgaris, chronic telogen effluvium, erosive oral lichen planus, and dystrophic epidermolysis bullosa. Regenerative medicine was found to be an effective treatment option in all of these studies, along with other methods. The regenerative medicine techniques investigated in this study comprised the transplantation of autologous epidermal melanocyte/keratinocyte cells, isolated melanocyte transplantation, cell transplantation from hair follicle origins, melanocyte–keratinocyte suspension in PRP, conditioned media injection, a combination of PRP and basic fibroblast growth factor, intravenous injection of mesenchymal stem cells, concentrated growth factor, stromal vascular fraction (SVF), a combination of PRP and SVF, and preserving hair grafts in PRP. Conclusion: Regenerative medicine holds promise as a treatment for specific dermatologic disorders. To validate our findings, it is recommended to conduct numerous clinical trials focusing on various skin conditions. In our study, we did not explore secondary skin lesions like scars or ulcers. Therefore, assessing the effectiveness of this treatment method for addressing these conditions would necessitate a separate study. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Numerous approaches have been developed to decelerate the aging process of facial skin. Synthetic fillers and cell-enriched fat grafts are the main procedures employed to fill wrinkles. Objective: The aim of this study was to evaluate the in vitro and in vivo safety and efficiency of a new process developed by SYMBIOKEN: the AmeaCell, which facilitates the extraction of the stromal vascular fraction (SVF) and the associated hypoxia pre-conditioned matrix to promote fat graft survival. Methods: The AmeaCell device allows the extraction from adipose tissue of SVF and pre-conditioned MatriCS and promotes a hypoxic environment. Experiments were carried out on human cells and then in mice. Results: Characterization of cells and MatriCS showed that after their extraction using the new process developed by SYMBIOKEN, the extracted cells expressed stem-cell markers. The presence of characteristic proteins and lipid fractions found in the adipose matrix were confirmed in MatriCS. Cobalt chloride treatment of the matrix using the AmeaCell device induced modifications in the matrix composition with a decrease in laminin and without collagen modification, both of which promote adhesion and differentiation of SVF or adipose-derived stromal cells. The combination of MatriCS and SVF (1 × 106 and 5 × 106, respectively) is safe and efficient to fill winkles induced by UVB irradiation. The cross-talk between MatriCS and SVF can act a durable filler compared to the filling performed using cells or matrix or fat alone, which need to be replaced frequently. Conclusion: These results indicate that the combination of MatriCS and SVF is safe and effective as a biological filler for achieving skin rejuvenation and wrinkle filling.

Given the recent evidence in the clinical application of regenerative medicine, mostly on integumentary systems, we focused our interests on recent bladder regeneration approaches based on mesenchymal stem cells (MSCs), platelet-rich plasma (PRP), and hyaluronic acid (HA) in the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS) in humans. IC/BPS is a heterogeneous chronic disease with not-well-understood etiology, characterized by suprapubic pain related to bladder filling and urothelium dysfunction, in which the impairment of immunological processes seems to play an important role. The histopathological features of IC include ulceration of the mucosa, edema, denuded urothelium, and increased detection of mast cells and other inflammatory cells. A deeper understanding of the molecular mechanism underlying this disease is essential for the selection of the right therapeutic approach. In fact, although various therapeutic strategies exist, no efficient therapy for IC/BPS has been discovered yet. This review gives an overview of the clinical and pathological features of IC/BPS, with a particular focus on the molecular pathways involved and a special interest in the ongoing few investigational therapies in IC/BPS, which use new regenerative medicine approaches, and their synergetic combination. Good knowledge of the molecular aspects related to stem cell-, PRP-, and biomaterial-based treatments, as well as the understanding of the molecular mechanism of this pathology, will allow for the selection of the right and best use of regenerative approaches of structures involving connective tissue and epithelia, as well as in other diseases. [ABSTRACT FROM AUTHOR]

Introduction: Medication-related osteonecrosis of the jaw (MRONJ) poses a significant challenge considering the absence of a "gold standard" treatment. Cell-based therapy and tissue engineering offer promising therapeutic alternatives. This study aimed to harness the regenerative properties of adipose-tissue stromal vascular fraction (AT-SVF) and leukocyte-platelet-rich fibrin (L-PRF) for MRONJ treatment. AT-SVF contains mesenchymal stromal cells (MSC) and endothelial progenitor cells (EPC), which promote bone formation, while the L-PRF scaffold can serve as a three-dimensional scaffold for the AT-SVF and support tissue healing through growth factor release. Materials and methods: The protocol involved applying autologous AT-SVF within an L-PRF matrix following surgical debridement. Age, gender, body mass index, comorbidities, underlying oncological condition, prescribed antiresorptive treatment: BP or DMB, antiresorptive treatment duration, antiresorptive treatment potential discontinuation, number of MRONJ lesion, MRONJ location, MRONJ stage, MRONJ trigger factor were assessed for each patient. Patients underwent the procedure and were monitored for a minimum of 6 months based on clinical, biological and medical imaging criteria. Results: Nine patients, with a total of ten MRONJ lesions, participated in the study. Six patients were female, and three were male, with a mean age of 68 ± 8 years. Four patients had multiple myeloma (MM), three had metastatic breast cancer, and two had metastatic prostate cancer. Seven MRONJ cases were classified as stage II, and three were classified as stage III. Soft tissue completely healed within a month after treatment in nine cases, with no clinical improvement observed in the remaining case. During follow-up, no sign of MRONJ recurrence was observed. Tridimensional medical imaging revealed bone healing 6 months after the surgical procedure. Immunophenotyping confirmed the presence of MSC and EPC in the AT-SVF: 12,6 ± 4,5% CD31+, 20.5 ± 7,8% CD34+, 34,4 ± 7,3% CD146+ and 54,6 ± 7,4% CD45+. Conclusion: This prospective study introduces a potential new treatment approach for MRONJ using autologous AT-SVF within an L-PRF scaffold. Our results are encouraging and suggest the need for further investigation with a larger patient cohort to better understand the underlying mechanisms. [ABSTRACT FROM AUTHOR]

Introduction: Medication-related osteonecrosis of the jaw (MRONJ) poses a significant challenge considering the absence of a “gold standard” treatment. Cell-based therapy and tissue engineering offer promising therapeutic alternatives. This study aimed to harness the regenerative properties of adipose-tissue stromal vascular fraction (AT-SVF) and leukocyte-platelet-rich fibrin (L-PRF) for MRONJ treatment. AT-SVF contains mesenchymal stromal cells (MSC) and endothelial progenitor cells (EPC), which promote bone formation, while the L-PRF scaffold can serve as a three-dimensional scaffold for the AT-SVF and support tissue healing through growth factor release.Materials and methods: The protocol involved applying autologous AT-SVF within an L-PRF matrix following surgical debridement. Age, gender, body mass index, comorbidities, underlying oncological condition, prescribed antiresorptive treatment: BP or DMB, antiresorptive treatment duration, antiresorptive treatment potential discontinuation, number of MRONJ lesion, MRONJ location, MRONJ stage, MRONJ trigger factor were assessed for each patient. Patients underwent the procedure and were monitored for a minimum of 6 months based on clinical, biological and medical imaging criteria.Results: Nine patients, with a total of ten MRONJ lesions, participated in the study. Six patients were female, and three were male, with a mean age of 68 ± 8 years. Four patients had multiple myeloma (MM), three had metastatic breast cancer, and two had metastatic prostate cancer. Seven MRONJ cases were classified as stage II, and three were classified as stage III. Soft tissue completely healed within a month after treatment in nine cases, with no clinical improvement observed in the remaining case. During follow-up, no sign of MRONJ recurrence was observed. Tridimensional medical imaging revealed bone healing 6 months after the surgical procedure. Immunophenotyping confirmed the presence of MSC and EPC in the AT-SVF: 12,6 ± 4,5% CD31+, 20.5 ± 7,8% CD34+, 34,4 ± 7,3% CD146+ and 54,6 ± 7,4% CD45+.Conclusion: This prospective study introduces a potential new treatment approach for MRONJ using autologous AT-SVF within an L-PRF scaffold. Our results are encouraging and suggest the need for further investigation with a larger patient cohort to better understand the underlying mechanisms.

Background: The appearance of skin scars is known as one of the main side effects of skin burns. Stromal vascular fraction (SVF), as a rich source of cell populations with tissue regeneration properties, plays an important role in the healing of skin lesions. Fractional CO2 lasers have occupied a special place in treating skin lesions, particularly skin scars, since their introduction. Our study aimed to compare the combination of SVF and fractional CO2 laser with fractional CO2 laser alone in the treatment of burn scars. Method: This double-blind clinical trial study was conducted on ten patients with burn scars that were treated three times with a fractional CO2 laser at site of burn lesions, and one of the two areas studied was randomly injected with SVF. Two months after completion of the procedure, patients' scars were assessed using the Vancouver scar scale (VSS), biometric criteria, and physician and patient satisfaction ratings. Results: The results confirmed a significant improvement in VSS, cutometry, R7 criteria, complete density sonography, and skin density sonography in the fractional CO2 laser-treated group. The VSS criteria, epidermal thickness sonography, complete density sonography, and skin density sonography in the group treated with the combination of fractional CO2 laser and SVF also showed significant improvement. The VSS criteria and melanin index of Mexameter in the group treated with SVF in combination with fractional CO2 laser were significantly better than the group treated with fractional CO2 laser alone. Also, physician and patient satisfaction in the group treated with SVF injection in combination with fractional CO2 laser was significantly higher than the other group. Conclusion: The results confirm the efficacy of SVF injection in combination with fractional CO2 laser in the treatment of burn scars and can be considered as a treatment option for better management of these lesions. Trial registration: The study protocol was retrospectively registered at Iranian Registry of Clinical Trials with code: IRCT20210515051307N1, Registration date: 2021-11-14, URL: https://www.irct.ir/trial/56337. [ABSTRACT FROM AUTHOR]

Mechanically processed stromal vascular fraction (mSVF) is a highly interesting cell source for regenerative purposes, including wound healing, and a practical alternative to enzymatically isolated SVF. In the clinical context, SVF benefits from scaffolds that facilitate viability and other cellular properties. In the present work, the feasibility of methacrylated gelatin (GelMA), a stiffness-tunable, light-inducible hydrogel with high biocompatibility is investigated as a scaffold for SVF in an in vitro setting. Lipoaspirates from elective surgical procedures were collected and processed to mSVF and mixed with GelMA precursor solutions. Non-encapsulated mSVF served as a control. Viability was measured over 21 days. Secreted basic fibroblast growth factor (bFGF) levels were measured on days 1, 7 and 21 by ELISA. IHC was performed to detect VEGF-A, perilipin-2, and CD73 expression on days 7 and 21. The impact of GelMA-mSVF on human dermal fibroblasts was measured in a co-culture assay by the same viability assay. The viability of cultured GelMA-mSVF was significantly higher after 21 days (p < 0.01) when compared to mSVF alone. Also, GelMA-mSVF secreted stable levels of bFGF over 21 days. While VEGF-A was primarily expressed on day 21, perilipin-2 and CD73-positive cells were observed on days 7 and 21. Finally, GelMA-mSVF significantly improved fibroblast viability as compared with GelMA alone (p < 0.01). GelMA may be a promising scaffold for mSVF as it maintains cell viability and proliferation with the release of growth factors while facilitating adipogenic differentiation, stromal cell marker expression and fibroblast proliferation. [ABSTRACT FROM AUTHOR]

Background: The efficacy and safety evaluation of the transplantation of autologous fat, platelet-rich plasma (PRP) and stromal vascular fraction (SVF) in acne scars has not been completely unified. This article will analyze and process the data of the included studies through evidence-based medicine to evaluate the efficacy and safety of autologous fat grafting, PRP and SVF for acne scar treatment, so as to provide treatment basis and strategy for the clinical treatment of acne scars. Methods: We searched the PubMed, Embase, Cochrane Library databases, CNKI, Wanfang and CQVIP databases for studies published during the time between the establishment of the databases through October 2022. We included studies that report autologous fat grafting, SVF and PRP for patients with acne scars. We excluded repeated publication, researches without full text, incomplete information or inability to conduct data extraction and animal experiments, case report, reviews and systematic reviews. STATA 15.1 software was used to analyze the data. Results: The findings showed that fat grafting had excellent improvement, marked improvement, moderate improvement and mild improvement rates of 36%, 27%, 18% and 18%, respectively, PRP had excellent improvement, marked improvement, moderate improvement and mild improvement rates of 0%, 26%, 47% and 25%, respectively, and the SVF had excellent improvement, marked improvement, moderate improvement and mild improvement rates of 73%, 25%, 3% and 0%, respectively. Additionally, the pooled results showed that there was no significant difference between PRP treatment and pre-treatment in Goodman and Baron scale score. However, Shetty et al. reported that Goodman and Baron scale score after fat grafting was significantly lower than pre-treatment. The results also showed that after fat grafting treatment, incidence of pain after fat grafting was 70%. After PRP treatment, in addition to pain (17%), there is a higher probability of postinflammatory hyperpigmentation (17%) and hematoma (6%). After SVF treatment, the incidence of postinflammatory hyperpigmentation and hematoma was all 0%. Conclusion: Autologous fat grafting, PRP and SVF are effective for the treatment of acne scars, and the safety of autologous fat grafting, PRP and SVF is acceptable. Autologous fat grafting and SVF may be a better treatment for acne scars than PRP. However, this hypothesis still needs to be tested in the future large randomized controlled trials. 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 www.springer.com/00266. [ABSTRACT FROM AUTHOR]

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Air pollution is one of the most important problems that threaten life today. Different housing textures in the city were examined in terms of air pollution values (emission values) and geographical variables that trigger air pollution (pressure, altitude, wind, temperature) and physical variables (natural gas consumption, coal consumption and Sky View Factor). Spatial analyzes of the variables were done with Arcgis. SPSS was used for statistical analysis. Correlation analysis was used to understand the difference between housing patterns variables, Kruskal Wallis to understand the difference between housing patterns, and Posthoc – Games Howell analysis at 95% confidence level to reveal which parameters were different. Block-type housing pattern is significantly more dense than other housing patterns in terms of emission values and pressure values, and has a significantly more intense value in natural gas and coal consumption than other housing patterns, except shanty housing. Gated community type housing texture has a significantly more intense value in terms of wind speed than other housing patterns. As a matter of fact, the wind speed was found to be less than 3 m/s. The shanty housing pattern has a significantly more intense value than other housing patterns in terms of altitude and fuel consumption. Detached house texture has a significantly higher value of O3, temperature and SVF than other housing patterns. Considering the urban transformation areas in Erzurum, it is clear that local governments, city planners and landscape architects should produce site-specific urban design proposals, taking into account the natural conditions. [ABSTRACT FROM AUTHOR]

Abstract Background In knee osteoarthritis, progressive degeneration of the articular cartilage surface produces disability and chronic pain. Intra-articular injections of stromal vascular fraction (SVF) could be an innovative approach to manage patients with early knee osteoarthritis. Methods Between June 2019 and November 2020, 123 patients were recruited to receive intra-articular injection of SVF. Radiographic evidence of degenerative joint disease was classified according to Kellgren and Lawrence grades. Knee injury and osteoarthritis outcome score (KOOS) and visual analog scale (VAS) were collected preoperatively, at 1 month, and after 6 months from injection. Results There was a statistically significant improvement of KOOS and VAS of all patients to 6 months (p

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

Background: Diabetic nephropathy (DN), a common complication of type 2 diabetes (T2D), significantly contributes to end-stage kidney disease (ESKD). Despite conventional treatments aimed at slowing disease progression, there is a pressing need for novel therapies. This study evaluates the potential therapeutic impact of adipose tissue derived stromal vascular fraction (SVF) on early diabetic nephrotoxicity in a rat model., Materials and Methods: Thirty-one male albino rats were divided into control and diabetic groups, with the latter further split into untreated (T2Da) and SVF-treated (T2Db) subgroups. Biochemical, histological, immunohistochemical, and morphometric analyses were conducted., Results: We demonstrated that SVF treatment reduced oxidative stress, lowered serum creatinine, and improved renal architecture by mitigating fibrosis and cellular infiltration, suggesting enhanced tissue regeneration and reduced inflammation. SVF also facilitated cellular repair, indicated by increased endothelial cell proliferation and reduced glomerular damage., Conclusions: This study underscores SVF's potential as a promising regenerative approach for managing early-stage DN, warranting further research to elucidate its mechanisms.

Background: There is no definitive solution for the treatment of striae distensae (SD), and effectiveness of each treatment method remains controversial. We aimed to investigate and compare the efficacy of the combination of Erbium YAG (Er:YAG) laser and stromal vascular fraction (SVF), the combination of Er:YAG laser and platelet-rich plasma (PRP) and Er:YAG laser plus saline in the treatment of SD., Materials and Methods: In 12 participating patients with at least three lesions (36 lesions in total), each lesion was treated with an Er:YAG laser. SVF was randomly injected intradermally for the first lesion, PRP for the second lesion, and normal saline as placebo for the third lesion. Treatment duration was one session, and the safety and efficacy of the treatment was assessed 3 months later using the following items: evaluation of biometric parameters including corneometery, erythema, melanin, tewametery, color, cutometery, complete thickness, epidermal thickness, dermal thickness, complete density, epidermal density, and dermal density; assessment of patient and physician satisfaction using Likert score; and recording of adverse effects of treatment., Results: The study involved 12 patients (evaluating 36 lesions in total), predominantly women (83%), with an average age of 39.16 years. The analysis revealed significant improvements in biometric indices, including complete thickness, epidermal thickness, dermal thickness, and R5 cutometer readings across all groups after the intervention. Notably, the SVF and PRP groups showed statistically significant enhancements in dermal and complete density compared to the placebo group. The SVF group demonstrated a significant increase in epidermal density (from 45.95 to 51.19, p = 0.001), unlike the PRP and placebo groups which showed nonsignificant changes. Comparing the average changes in biometric factors, the SVF group exhibited significantly greater increases in complete thickness, dermal thickness, complete density, epidermal density, and dermal density than the other groups. Both patient and physician satisfaction scores were highest in the SVF group (p = 0.001), with no significant posttreatment complications reported., Conclusion: Our results showed that the combination of Er:YAG laser and SVF injection could be considered an effective and safe treatment method in the treatment of SD., Trial Registration: IRCT20200127046282N14., (© 2025 The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

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

Although canonical Wnt signaling pathway activation was shown to negatively regulate adipogenesis, recent investigations suggest that Wnt pathway effectors TCF7L2 and β-catenin (β-cat) in adipose tissues are also involved in energy homeostasis during adulthood. In assessing the metabolic beneficial effect of GLP-1-based diabetes drugs in high-fat diet (HFD)-challenged mice, we observed that liraglutide treatment affected the expression of a battery of adipose tissue-specific genes, including those that encode adiponectin and leptin, mainly in epididymal white adipose tissue (eWAT). Fourteen-week HFD challenge repressed TCF7L2 and β-cat S675 phosphorylation in eWAT, while such repression was reversed by liraglutide treatment (150 μg/kg body weight daily) during weeks 10-14. In Glp1r-/- mice, liraglutide failed in stimulating TCF7L2 or β-cat in eWAT. We detected Glp1r expression in mouse eWAT and its level is enriched in its stromal vascular fraction (SVF). Mouse eWAT-SVF showed reduced expression of Tcf7l2 and its Tcf7l2 level could not be stimulated by liraglutide treatment; while following adipogenic differentiation, rat eWAT-SVF showed elevated Tcf7l2 expression. Direct in vitro liraglutide treatment in eWAT-SVF stimulated CREB S133, β-cat S675 phosphorylation, and cellular cAMP level. Thus, cAMP/β-cat signaling cascade can be stimulated by liraglutide in eWAT via GLP-1R expressed in eWAT-SVF. [ABSTRACT FROM AUTHOR]

Background: Bone is naturally regenerable, with a high ability to repair itself. In massive segmental bone defect, bone cannot be repaired independently. Therefore, it is necessary to give a bone graft to promote the healing process. To date, autografts are the gold standard for bone grafts. However, some of the reported complications reported have led to auto-bone transplants being often disregarded. Both autografts or allografts also have some issues. Therefore, in an effort to develop alternative treatments for correcting bone defects and their consequences, bone tissue engineering (BTE) has gained popularity and is nowadays being researched as a potential alternative in bone defect management. There are three fundamental components in BTE combined: biomaterials (scaffolds), mesenchymal stem cells (MSCs), and growth factors. The combination of these components is believed to help the healing process of bone defects. Methods: This work was an animal study involving twenty Wistar strain Rattus norvegicus. They were divided into five groups: negative group (normal rats), positive group (rats with the bone defect without intervention), K-P1 group (rats with bone defect given SVF and porous carbonated- hydroxyapatite (HA)application), K-P2 group (rats with bone defect given SVF and nanocrystalline-HA application) and K-P3 (rats with bone defect giving SVF a bovine-HA application). After 30 days, the rats were sacrificed, the biomarkers osteocalcin and BMP-2 were evaluated. Biomarkers were quantified using ELISA. Results: Both osteocalcin and BMP-2 biomarker expressions were higher in intervention group (with SVF and scaffolds application) compared to the positive group (with no SVF and scaffolds treatment). The combination of SVF and bovine HA was reported significantly to have the highest osteocalcin and BMP levels when compared with other groups Conclusions: A combined application of SVF and scaffolds could aid the healing process in murine models with bone defect, marked by increasing levels of osteocalcin and BMP-2.

Background: Nanofat grafting (NG) is a simple and cost-effective method of lipoaspirates with inter-syringe passages, to produce stromal vascular fraction (SVF) and isolate adipose-derived stem cells (ASCs). This represents a tremendous interest in the future clinical needs of tissue engineering. In this study, we optimized the NG technique to increase the yield of ASC extractions.Methods: We analyzed three groups of SVF obtained by 20, 30, and 40 inter-syringe passages. The control group was an SVF obtained by enzymatic digestion with Celase. We studied their cell composition by flow cytometry, observed their architecture by confocal microscopy, and observed immunomodulatory properties of the ASCs from each of the SVFs by measuring inflammatory markers of macrophages obtained by an ASC monocyte co-culture.Results: We have established the first cell mapping of the stromal vascular fraction of adipose tissue. The results showed that SVF obtained by 20 inter-syringe passages contains more statistically significant total cells, more cells expressing the ASC phenotype, more endothelial cells, and produces more CFU-F than the SVF obtained by 30 and 40 passages and by enzymatic digestion. Confocal microscopy showed the presence of residual adipocytes in SVF obtained by inter-syringe passages but not by enzymatic digestion. The functional study indicates an orientation toward a more anti-inflammatory profile and homogenization of their immunomodulatory properties.Conclusion: This study places mechanically dissociated SVF in the center of approaches to easily extract ASCs and a wide variety and number of other progenitor cells, immediately available in a clinical setting to provide both the amount and quality of cells required for decellularized tissues.

Abstract Background Recovery of muscle function after peripheral nerve injury is often poor, and this can be attributed to muscle fiber atrophy and cell death. In the current study, we have investigated the effects of stromal vascular fraction (SVF) on muscle cell apoptosis and its potential to preserve muscle tissue following denervation. Methods Rat gastrocnemius muscle was denervated by sciatic nerve transection. At 2 and 4 weeks after injury, muscles were examined histologically and apoptosis was measured using TUNEL assay and PCR array for a range of apoptotic genes. Additionally, an in vitro TNF-α apoptosis model was established using SVF cells co-cultured indirectly with primary rat myoblasts. Annexin V and TUNEL were used together with Western blotting to investigate the signaling pathways. Results Denervated muscles showed significantly higher TUNEL reactivity at 2 and 4 weeks following nerve injury, and an increased expression of caspase family genes, mitochondria-related apoptotic genes, and tumor necrosis factor family genes. In cultured rat primary myoblasts, Annexin V labeling was significantly increased at 12 h after TNF-α treatment, and this was followed by a significant increase in TUNEL reactivity at 48 h. Western blotting showed that caspase-7 was activated/cleaved as well as the downstream substrate, poly (ADP-ribose) polymerase (PARP). Co-culture of myoblasts with SVF significantly reduced all these measures of apoptosis. Bax and Bcl-2 levels were not changed suggesting that the TNF-α-induced apoptosis occurred via mitochondria-independent pathways. The protective effect of SVF was also shown in vivo; injections of SVF cells into denervated muscle significantly improved the mean fiber area and diameter, as well as reduced the levels of TUNEL reactivity. Conclusions This study provides new insights into how adipose tissue-derived cells might provide therapeutic benefits by preserving muscle tissue.

Background: In knee osteoarthritis, progressive degeneration of the articular cartilage surface produces disability and chronic pain. Intra-articular injections of stromal vascular fraction (SVF) could be an innovative approach to manage patients with early knee osteoarthritis. Methods: Between June 2019 and November 2020, 123 patients were recruited to receive intra-articular injection of SVF. Radiographic evidence of degenerative joint disease was classified according to Kellgren and Lawrence grades. Knee injury and osteoarthritis outcome score (KOOS) and visual analog scale (VAS) were collected preoperatively, at 1 month, and after 6 months from injection. Results: There was a statistically significant improvement of KOOS and VAS of all patients to 6 months (p < 0.05). The mean KOOS before injection was 51.4 ± 16.5, after 1 month it was 75.5 ± 15.8, and at 6 months it was 87.6 ± 7.7. Stratifying the mean KOOS according to Kellgren–Lawrence Grades, the difference remained statistically significant (p < 0.05). The patients' mean VAS before injection was 6.5, after 1 month it was 3.5, and after 6 months it was 2.4. No complications were observed. Conclusions: Intra-articular knee injection of SVF is safe and effective to ameliorate the clinical and functional scores in patients with early knee osteoarthritis for 6 months. [ABSTRACT FROM AUTHOR]

Adipose tissue is an attractive source of stem cells due to its wide availability. They contribute to the stromal vascular fraction (SVF), which is composed of pre-adipocytes, tissue-progenitors, and pericytes, among others. Because its direct use in medical applications is increasing worldwide, new quality control systems are required. We investigated the ability of the Non-Equilibrium Earth Gravity Assisted Dynamic Fractionation (NEEGA-DF) method to analyze and separate cells based solely on their physical characteristics, resulting in a fingerprint of the biological sample. Adipose tissue was enzymatically digested, and the SVF was analyzed by NEEGA-DF. Based on the fractogram (the UV signal of eluting cells versus time of analysis) the collection time was set to sort alive cells. The collected cells (F-SVF) were analyzed for their phenotype, immunomodulation ability, and differentiation potential. The SVF profile showed reproducibility, and the alive cells were collected. The F-SVF showed intact adhesion phenotype, proliferation, and differentiation potential. The methodology allowed enrichment of the mesenchymal component with a higher expression of mesenchymal markers and depletion of debris, RBCs, and an extracellular matrix still present in the digestive product. Moreover, cells eluting in the last minutes showed higher circularity and lower area, proving the principles of enrichment of a more homogenous cell population with better characteristics. We proved the NEEGA-DF method is a "gentle" cell sorter that purifies primary cells obtained by enzymatic digestion and does not alter any stem cell function. [ABSTRACT FROM AUTHOR]

Background: Knee injection using either bone marrow aspirate concentrate (BMAC) or stromal vascular fraction (SVF) from adipose tissue has been shown to result in symptomatic improvement in patients with knee osteoarthritis (OA). It is still unclear whether one of these therapies is superior over the other. Purpose: To systematically report the clinical studies evaluating BMAC and SVF in the treatment of knee OA and to compare the clinical efficacy of these 2 injection therapies. Study Design: Meta-analysis; Level of evidence, 4. Methods: This meta-analysis was performed per the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines. Studies were included if they reported the clinical outcomes after a single BMAC or SVF injection in the knee joint of patients with OA. Studies evaluating preparations of culture-expanded stem cells were excluded. A random effects model was used; the clinical efficacy of BMAC or SVF injection was assessed using the standardized mean difference (SMD) and compared. Visual analog scale (VAS) scores for pain and Western Ontario and McMaster Universities Osteoarthritis (WOMAC) knee index were the primary outcomes. The level of statistical significance was set at P <.05. Results: Ten studies and 472 patients with knee OA who received either BMAC (233 patients) or SVF (239 patients) were included. Patients who received an injection had improved VAS outcomes (mean ± SD): from 5.8 ± 1.3 to 2.6 ± 17 for BMAC and from 6.4 ± 1.4 to 3.4 ± 0.5 for SVF. They also experienced significantly reduced pain (SMD [VAS], 2.6 for BMAC and 3.4 for SVF) and improved function (SMD [WOMAC], 1.4 for BMAC and 1.2 for SVF). However, the SVF injection had a significantly greater effect on pain reduction than did the BMAC injection (P <.0001). Based on WOMAC, the clinical effect of BMAC versus SVF knee injection in patients with knee OA was equivalent (P =.626). Results were limited by the presence of publication bias as well as variability in the preparation methods utilized in the BMAC and SVF injection protocols. Complications were reported in 50% of the BMAC studies (knee stiffness, persistent knee swelling) and 67% of the SVF studies (knee swelling, knee pain, positive SVF cultures without symptoms of infection, and bleeding at the abdominal harvest site). Conclusion: A single BMAC or SVF injection into the knee joint of patients with OA resulted in symptomatic improvement at short-term follow-up. However, SVF seemed to be more effective than did BMAC in the reduction of knee pain. There was significant variation in the BMAC and SVF injection preparation techniques used across the studies and a lack of stratification of outcomes based on the radiologic classification of OA. Therefore, these results should be taken with caution. [ABSTRACT FROM AUTHOR]