Combined Stromal Vascular Fraction and Fractional CO2 Laser Therapy for Hypertrophic Scar Treatment: A Systematic Review and Meta-Analysis.

BACKGROUND: Hypertrophic scars (HTSs) result from aberrant wound healing processes, leading to raised, thickened tissue with functional discomfort and cosmetic concerns. Current treatments, including corticosteroid injections and laser therapy, have limitations. Stromal vascular fraction (SVF) therapy and CO2 laser treatment offer promising avenues, with SVF therapy showing regenerative potential and CO2 laser therapy promoting precise tissue removal and wound healing. This study aims to investigate the combined application of SVF therapy and CO2 laser treatment for HTS, aiming to enhance treatment efficacy, tissue remodeling, and aesthetic outcomes, ultimately improving patient satisfaction in HTS management. METHOD: PubMed, Scopus, Embase, and Web of Science databases have been searched for relevant studies. The "R" software (version 4.3.1) along with the "tidyverse" and "meta" statistical packages utilized to analyze data related to the efficiency of this combined method. A random-effects model was fitted to the data. For each study, continuous outcomes were pooled by calculating the standardized mean difference, along with their 95% confidence intervals. The assessment of heterogeneity utilized the I2 and chi-squared tests, applying the random effect model. RESULTS: Six articles fulfilled our inclusion criteria and were included in our review. Results from the pooled analysis of Vancouver Scar Scale (VSS) scores across three included studies indicated a significant impact of the SVF+CO2 method on VSS scores post-treatment (SMD=-3.0144; 95% CI:-4.3706 to -1.6583, p<0.0001). However, analysis of transepidermal water loss levels before and after treatment showed no significant difference (SMD=-2.7603; 95% CI: -6.8729 to 1.3522; p=0.1883). Comparatively, in a pooled analysis of two studies, the combined SVF+CO2 method demonstrated superior efficacy in VSS scores compared to other methods (SMD= -1.3573; 95% CI: -2.2475 to -0.4672, p = 0.0028), with moderate heterogeneity across studies (I^2=23.0%, p = 0.2545). CONCLUSION: The combined application of SVF and CO2 laser treatment shows significant promise in improving hypertrophic scars' appearance and texture. The SVF+CO2 method demonstrates superior efficacy compared to other modalities, suggesting its potential as a valuable therapeutic approach for hypertrophic scar management. 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 .

Mesenchymal Stem Cells and Secretome as a New Possible Approach to Treat Cartilage Damage: An In Vitro Study.

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.

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.

Guided SEFFI and CaHA: A Retrospective Observational Study of an Innovative Protocol for Regenerative Aesthetics.

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.

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.

Comparison of stromal vascular fraction cell composition between Coleman fat and extracellular matrix/stromal vascular fraction gel.

As a mechanically condensed product of Coleman fat, extracellular matrix/stromal vascular fraction gel (ECM/SVF-gel) eliminates adipocytes, concentrates SVF cells, and improves fat graft retention. This study aims to compare SVF cell composition between Coleman fat and ECM/SVF-gel. Matched Coleman fat and ECM/SVF-gel of 28 healthy women were subjected to RNA-seq, followed by functional enrichment and cell-type-specific enrichment analyses, and deconvolution of SVF cell subsets, reconstructing SVF cell composition in the transcriptome level. ECM/SVF-gels had 9 upregulated and 73 downregulated differentially expressed genes (DEGs). Downregulated DEGs were mainly associated with inflammatory and immune responses, and enriched in fat macrophages. M2 macrophages, resting CD4+ memory T cells, M1 macrophages, resting mast cells, and M0 macrophages ranked in the top five most prevalent immune cells in the two groups. The proportions of the principal non-immune cells (e.g., adipose-derived stem cells, pericytes, preadipocytes, microvascular endothelial cells) had no statistical differences between the two groups. Our findings reveal ECM/SVF-gels share the same dominant immune cells beneficial to fat graft survival with Coleman fat, but exhibiting obvious losses of immune cells (especially macrophages), while non-immune cells necessary for adipose regeneration might have no significant loss in ECM/SVF-gels and their biological effects could be markedly enhanced by the ECM/SVF-gel's condensed nature.

Regenerative medicine in the treatment of specific dermatologic disorders: a systematic review of randomized controlled clinical trials.

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.

Role of Autologous Micro-Fragmented Adipose Tissue in Osteoarthritis Treatment.

Osteoarthritis (OA) is the most common complex musculoskeletal disorder, resulting from the degeneration of the articular cartilage and characterized by joint pain and dysfunction that culminate in progressive articular cartilage loss. We present our experience in the management of hip and knee OA by means of the intra-articular injection of fat micrograft, describing our approach, which was developed from the belief in the powerful reparative effect of autologous fat graft on damaged tissue, as well as its natural lubricating effect on the joints. Inclusion criteria were as follows: men and women, aged 20 to 80 years, that referred articular pain of the hips and/or knees, showing initial-stage degenerative OA. From October 2018 to July 2023, a total of 250 patients underwent treatment with the Sefficare® device (SEFFILINE srl, Bologna, Italy). The Superficial Enhanced Fluid Fat Injection device was used to perform autologous regenerative treatments in a safe, standardized, easy, and effective way on 160 women, 64%, and 90 men, 36%. A total of 190 procedures (76%) involved the knees, with 20 patients who were bilaterally treated, while 60 procedures, all unilateral, involved the hips (24%). The mean age at treatment was 52.4 years. Before treatment, each patient had undergone X-rays and Magnetic Resonance Imaging (MRI) of the painful hip/knee to evaluate and grade the articular OA. Postoperatively, each patient was assessed after one, three, six, and twelve months. The donor site postoperative course was uneventful other than minimal discomfort. Clinically, the ROM (range of motion) of the treated knee/hip increased an average of 10 degrees 3 months after treatment, but the stiffness was reduced, as reported by the patients. The VAS (Visual Analog Scale) was submitted at 3, 6, and 12 months, demonstrating a progressive reduction of pain, with the best score obtained at six months postoperatively. In total, 85% of patients were satisfied one year after treatment, with a considerable improvement in pain and quality of life. The satisfactory outcome of this minimally invasive procedure indicates that the intra-articular injection of fat micrograft can replace or considerably delay the need for the classical major joint replacement surgery, thanks to its impact on the quality of life of patients and financial cost.

Immediate SVF-Gel Injection Reduced Incision Scar Formation: A Prospective, Double-Blind, Randomized, Self-control Trial.

BACKGROUND: Skin incision scars are cosmetically displeasing; the effects of current treatments are limited, and new methods to reduce scar formation need to be found. OBJECTIVE: We sought to determine whether immediate postoperative injection of stromal vascular fraction gel (SVF-gel) could reduce scar formation at skin incision sites. METHODS: A prospective, randomized, double-blind, self-controlled trial was conducted in patients who underwent breast reduction. SVF-gel was intradermally injected into the surgical incision on one randomly selected side, with the other side receiving saline as a control. At the 6-month follow-up, the incision scars were evaluated using the Vancouver scar scale (VSS) and visual analog scale (VAS). Antera 3D camera was used for objective evaluation. RESULTS: The VSS score and VAS score were significantly different between the SVF-gel-treated side (3.80 ± 1.37, 3.37±1.25) and the control side (5.25 ± 1.18, 4.94 ± 1.28). Moreover, the SVF-gel-treated side showed statistically significant improvements in scar appearance, based on evidences from Antera 3D camera. LIMITATIONS: This was a single-center, single-race, and single-gender study. Furthermore, the results were available only for the 6-month interim follow-up period. CONCLUSION: Postoperative immediate SVF-gel injection in surgical incisions can reduce scar formation, and exert a preventive effect on scars. LEVEL OF EVIDENCE I: Evidence obtained from at least one properly designed randomized controlled trial. 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 .

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.

Isolation of Human Adipose-Derived Stromal/Stem Cells from Lipoaspirates.

Adipose tissue is an abundant and accessible source of stem cells with multipotent properties suitable for tissue engineering and regenerative medical applications. Adipose-derived stromal/stem cells (ASCs) have been widely used in tissue engineering and cell therapy. In addition, the clinical application of ASCs in the treatment of inflammation and injury has been proven a success. Here, we describe methods from our own laboratory and the literature for the isolation and expansion of Adipose-derived stromal/stem cells (ASCs). We present a large-scale procedure suitable for processing >100 mL volumes of lipoaspirate tissue specimens by collagenase digestion, a related procedure suitable for processing adipose tissue aspirates without digestion, and a procedure suitable for intact human adipose tissue, such as buccal fat pads in the maxillofacial region.

Isolation of Human Adipose-Derived Stem Cells.

Human adipose-derived stromal/stem cells (hASCs) are a promising source of adult stem cells used in numerous applications in regenerative medicine. We present the protocols from our laboratory for isolating and expanding hASCs. The isolation of hASCs involves the enzymatic digestion of adipose tissue and subsequent culturing of the isolated cells.

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

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

Treatment of medication-related osteonecrosis of the jaw with cell therapy.

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.

Exploring Preclinical Experiments with Different Fat Types for Autologous Fat Grafting.

BACKGROUND: Autologous fat transplantation has been a cornerstone of tissue regeneration for decades. However, there is no standardized selection system or criteria for fat graft selection, often relying heavily on the surgeon's experience. OBJECTIVES: This study aimed to investigate various types of fat derivatives, both in vitro and in vivo at the same condition. METHODS: We collected traditional fat granules of different sizes and SVF-gel, evaluating the viability of ADSCs isolated from them and their performance after grafting into mice. RESULTS: Large fat granules exhibited more complete adipocyte structures, and the isolated ADSCs demonstrated superior differentiation, proliferation, and secretion capacities. They also showed excellent volume retention after 12 weeks. In contrast, ADSCs isolated from SVF-gel displayed lower vitality. However, grafts from SVF-gel exhibited the highest volume maintenance rate among the four groups after 12 weeks, closely resembling normal adipose tissue and displaying significant vascularization. Compared to large fat granule and SVF-gel group, medium and small fat granule grafts exhibited lower volume retention and less angiogenesis. CONCLUSIONS: Through preclinical studies, the flexible clinical use of different fat grafts can be tailored to their unique characteristics. LEVEL OF EVIDENCE I: 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 .

The Model of Interstitial Cystitis for Evaluating New Molecular Strategies of Interstitial Regeneration in Humans.

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.

The Evolution and Future Trends of Stromal Vascular Fraction: A Bibliometric Analysis.

The heterogeneous population of cells obtained from processed adipose tissue, known as stromal vascular fraction (SVF), exhibits immunomodulatory and angiogenic properties. The therapeutic efficacy of SVF has been substantiated in numerous diseases, instilling hope for its clinical application as a cellular therapy. This study aims to provide a comprehensive analysis of the scholarly literature on SVF, including its worldwide progression, highlighting significant literatures, temporal development, research clusters, current active topics, and emerging trends. The combination of CiteSpace, HistCite Pro, and VOS Viewer tools was used to analyze the SVF literature. The overall panorama of the field is elucidated in terms of publication count, timeline, institutional distribution, journal coverage, and authors' contributions. In addition, this analysis explores the literature and keywords through the lens of co-occurrence, citation, and co-citation frequencies. Clustering algorithms are used to track the trajectory of the literature further, providing insight into its development. The findings offer a comprehensive overview of the progress made in the SVF field, highlighting distinct phases of development: the "Seedling period" from 1980 to 2010, the "Panicle period" from 2011 to 2016, and the "Flowering period" from 2017 to 2023. Within these periods, the evolution of 10 clusters is unraveled, encompassing topics such as vascular disease, CD34 expression, adipose tissue macrophage in 2013, cell-assisted lipotransfer, and knee osteoarthritis. In summary, this bibliometric study, conducting a quantitative analysis of publications in SVF research, encompasses a global overview of research, an analysis of pivotal literature in the field, research hotspots, and emerging frontiers.

Positive effects of hypoxic preconditioning of the extracellular matrix and stromal vascular fraction from adipose tissue.

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.

A Novel Intervention That Prevents Vocal Fold Scarring.

OBJECTIVES: We evaluated the preventive efficacy of stromal vascular fraction (SVF) for vocal fold scar in a rabbit model. STUDY DESIGN: Animal model. METHODS: The study included 40 male New Zealand white rabbits: 20 received vocal fold scar surgery served as normal controls (control group). The other 20 received the same vocal fold scar surgery with SVF injection (SVF group) Histological and high-speed video analyses of vocal fold vibration were performed 4 weeks after scar surgery and SVF injection. The maximum amplitude of vocal fold vibration was used to assess vocal fold vibration. A real-time PCR study was also performed to evaluate the scar regeneration and remodeling including TGF-ß1, IL-6, procollagen-1, MMP-2, 9, and HAS-2, 3. RESULTS: Vocal fold vibration analyses indicated that the maximum amplitude differences in the vibration of the SVF group were significantly higher than the control group. The histological findings showed that the collagen density ratio were significantly lower in the SVF group compared to the control group. Real-time Polymerase Chain Reaction (PCR) study showed significant increases of MMP-2, 9 and HAS-2, 3, and a decrease of TGF-ß1, IL-6, procollagen-1 in the SVF group compared to the control group. CONCLUSIONS: Based on the vocal fold vibration study, histological findings, and real-time PCR study, SVF injection showed preventive activity and improvement of vocal fold vibration for vocal fold scar in a rabbit model.