High body mass index (BMI), encompassing overweight and obesity, is a well-established risk factor for developing breast cancer (BC). The underlying mechanisms linking elevated BMI to increased BC risk involve metabolic reprogramming and chronic inflammatory microenvironments regulated by cellular networks within breast white adipose tissue (WAT). However, the complicated landscape and specific cell chat leading to BC-related adipose microenvironment remained unclear.

We unveiled a comprehensive cell atlas by employing single-cell (N = 27) and single-nuclei (N = 6) transcriptomics to address dynamic changes of immune and stromal cell components within WAT in high BMI population. Bulk RNA-seq data sets were used for validation.

Characteristics of adipose-infiltrating tissue-resident macrophages (PVMs), APOD+γδ T cells, and mature FKBP5+ adipocytes in breast cancer women with high BMI were revealed, in terms of transcriptional genes, metabolism features, developmental trajectories and gene set enrichment analysis (GSEA). PVMs upregulated c-Maf combined with its co-activator CREB1 to increase TCA cycles. APOD+γδ T cells were found to elevate intracellular lipid metabolism, leading to poor clinical prognosis. Mature FKBP5+adipocytes served as an advanced adipogenesis mediator to promote tumor aggressiveness. In-depth analysis of cell-cell interactions uncovered a remodeling trend towards metabolic dysfunction and chronic inflammation in WAT with weight gain via EGF, CXCL, and CCL signalings.

These results provided a novel understanding of detailed and unbiased cellular landscape of WAT in breast cancer with high BMI from single-cell atlas perspective, uncovering interplays between breast adipose-infiltrating immune cells and stromal cells that promote progression of BC under high BMI conditions.

Metabolic syndrome (MetS), a conglomerate of dysregulated metabolic traits that vary between individuals, is partially driven by modern diets high in fat, sucrose, or fructose and their interactions with host genes in metabolic tissues. To elucidate the roles of individual tissues and cell types in diet-induced MetS, we performed single-cell RNA sequencing on the hypothalamus, liver, adipose tissue, and small intestine of mice fed high-fat high-sucrose (HFHS) or fructose diets. We found that hypothalamic neurons were sensitive to fructose, while adipose progenitor cells and macrophages were responsive to HFHS. Ligand-receptor analysis revealed lipid metabolism and inflammation networks among peripheral tissues driven by HFHS, while both diets stimulated synaptic remodeling within the hypothalamus. mt-Rnr2, a top responder to both diets, mitigated diet-induced MetS by stimulating thermogenesis. Our study demonstrates that HFHS and fructose diets have differential cell type and network targets but also share regulators such as mt-Rnr2 to affect MetS risk.

Heart failure (HF) represents the terminal stage of cardiovascular disease and remains a leading cause of mortality. Epidemiological studies indicate a high prevalence and mortality rate of HF globally. Current treatment options primarily include pharmacological and non-pharmacological approaches. With the development of mesenchymal stem cell (MSC) transplantation technology, increasing research has shown that stem cell therapy and exosomes derived from these cells hold promise for repairing damaged myocardium and improving cardiac function, becoming a hot topic in clinical treatment for HF. However, this approach also presents certain limitations. This review summarizes the mechanisms of HF, current treatment strategies, and the latest progress in the application of MSCs and their exosomes in HF therapy.

Autologous fat grafting is increasingly used in plastic, reconstructive, and esthetic surgery. Cryopreservation offers a promising solution for the long-term storage of adipose tissue, enabling multiple grafting sessions while minimizing patient discomfort associated with repeated liposuction for fat harvesting. This systematic review aims to analyze the current literature focusing on factors that influence the outcome of cryopreservation, including the use of cryoprotectants, the cooling and warming rate, the storage temperature, and the enrichment of cryopreserved fat grafts. A systematic search of the PubMed/MEDLINE database up to November 2024 was performed, including original preclinical and clinical studies written in English describing the cryopreservation of unprocessed or mechanically processed adipose tissue (macrofat, microfat, or nanofat). Eligible articles needed to describe the applied cryopreservation protocol, at least the storage temperature. Studies on cryopreservation of adipose-derived stem cells (ASCs), stromal vascular fraction, microvascular fragments, and other isolated components of adipose tissue were excluded. Data on cryoprotectants, cooling and warming rates, storage temperature, and eventual supplementation or enrichment of frozen fat were collected. Of the 679 records identified, 59 met the inclusion criteria. Adipose tissue cryopreservation at -80°C with a cryoprotectant, controlled slow cooling, and fast warming represented the most often applied protocol with encouraging outcomes in maintaining tissue survival and histological structure. Several studies indicated that the supplementation of frozen adipose tissue with ASCs improves tissue survival. Taken together, existing studies present diverse, and to some extent, conflicting results regarding cryopreservation protocols and their effects on adipose tissue viability. Hence, the ideal cryopreservation protocol for autologous fat remains to be established. Moreover, tailored protocols may be necessary for the cryopreservation of fat derivatives, such as nanofat.

Autologous fat grafting is widely used in reconstructive surgery and its use is increasing in different areas of regenerative medicine. This study evaluates the impact of elliptical lipoaspirate activation on adipose tissue grafting outcomes, focusing on scar-related pain reduction, improved scar characteristics, and increased tissue elasticity, comparing these outcomes with the traditional Coleman method.

This randomized double-blinded clinical trial study was conducted at the Humanitas Research Hospital in Milan from October 2022 to December 2023. Forty-three women aged 18-75 undergoing second-stage breast reconstruction were enrolled. The control group (19 patients) received the Coleman technique, while the study group (24 patients) underwent an additional elliptically oriented centrifugation. Method for evaluations included the Visual Analog Scale (VAS) for pain, Range of Movement (ROM), the Patient and Observer Scar Assessment Scale (POSAS), and shear wave elastography for tissue elasticity.

Both groups showed significant improvements over time. The case group demonstrated a greater decrease in VAS scores at 3 months (p = 0.015). POSAS scores were consistently better in the elliptical lipoaspirate activation group, significantly improving scar pruritus, pain, color, stiffness, thickness, and irregularity. Total POSAS score for both patient and observer scales were statistically higher for the case group at 12 months (p = 0.009 and p = 0.003, respectively). Elastography showed higher tissue softness in the case group at 6 months (p = 0.015) and 12 months (p = 0.0005). Tissue hardness, measured with elastography, was significantly lower for the case group at 12 months (p = 0.003).

The elliptical lipoaspirate activation technique significantly enhances clinical outcomes, reducing pain and improving scar quality and tissue elasticity compared to the standard Coleman method.

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Hip osteoarthritis constitutes a prevalent condition among individuals aged 55 and above, serving as one of the primary triggers for joint discomfort and impairment, and marking a substantial origin of chronic pain particularly affecting the elderly population. Our article provides an exhaustive summary of the mechanisms of action, therapeutic efficacy, and potential adverse consequences associated with novel therapeutic modalities including glucocorticoids, hyaluronic acid, platelet-rich plasma, mesenchymal stem cells, and stromal vascular fraction. Concurrently, we conducted a comprehensive evaluation of the clinical efficacy and potential applications of various medications.

In comparison to physical therapy, oral analgesics, and other nonsurgical modalities, intra-articular injection therapy is characterized by enhanced safety and greater efficacy. Moreover, when contrasted with surgical intervention, intra-articular injection demonstrates a lower degree of invasiveness and incurs fewer adverse reactions. Intra-articular treatments have shown excellent local efficacy while significantly minimizing adverse reactions in patients. These methods hold significant potential for development but require comprehensive research and thorough discussion within the academic community.

Adipose-derived stem cells (ADSCs) are known to promote angiogenesis and adipogenesis. However, their limited ability to efficiently target and integrate into specific tissues poses a major challenge for ADSC-based therapies. In this study, we identified a seven-amino acid peptide sequence (P7) with high specificity for ADSCs using phage display technology. P7 was then covalently conjugated to decellularized adipose-derived matrix (DAM), creating an "ADSC homing device" designed to recruit ADSCs both in vitro and in vivo. The P7-conjugated DAM significantly enhanced ADSC adhesion and proliferation in vitro. After being implanted into rat subcutaneous tissue, immunofluorescence staining after 14 days revealed that P7-conjugated DAM recruited a greater number of ADSCs, promoting angiogenesis and adipogenesis in the surrounding tissue. Moreover, CD206 immunostaining at 14 days indicated that P7-conjugated DAM facilitated the polarization of macrophages to the M2 phenotype at the implantation site. These findings demonstrate that the P7 peptide has a high affinity for ADSCs, and its conjugation with DAM significantly improves ADSC recruitment in vivo. This approach holds great potential for a wide range of applications in material surface modification.

The stromal vascular fraction (SVF) has been validated for enhancing tissue regeneration because of its concentration of multipotent cells and growth factors, and for mitigating inflammatory response due to its elimination of the majority of lipid droplets. However, it is difficult for fresh SVF to maintain bioactivity for a long period, and the loss of numerous tangible masses during preparation limits its application in repairing large volume defects. Here, we fabricated a self-assembly nanovesicle extruded from SVF (SVF-EVs) by mechanical shear and co-transplanted it with dermal microparticles to verify its potential for repairing large volume defects.

The SVF-EVs were prepared by removing the oil from adipose tissue followed by sequentially extruding SVF through membrane filters. The lipid content of SVF-EVs was compared with SVF using Oil Red O staining. The morphology and adipogenic-related protein of SVF-EVs were characterized. The pro-adipogenic potency of SVF-EVs in vitro was determined using Oil Red O staining of ADSCs, western blot, and qRT-PCR. In vivo, dermal particle grafts mixed with SVF-EVs were subcutaneously transplanted in nude mice and harvested after 4 and 6 weeks. By examining the weight and volume of grafts and histological staining, we explored the effect of SVF-EVs on adipose tissue regeneration and anti-inflammatory ability.

Our results showed that the removal rate of proceeding of SVF-EVs could remove 75.07 ± 2.80% lipid in SVF. The SVF-EVs displayed 100 ~ 150 nm sphere vesicles and contained pro-adipogenic protein. In vitro, SVF-EVs promote the synthesis of lipids in ADSCs. Besides, after co-transplanting of SVF-EVs, adipose regeneration was detected in vivo in the dermal particle grafts.

These findings revealed that extruding SVF into nanovesicles can effectively reduce the implantation of lipid droplets that cause inflammation, and co-transplanting SVF-EVs with dermal microparticles may be a considerable strategy for large volume defects repair.

We investigated the potential of adipose-derived stem cells (ADSCs) in preventing post-hepatectomy liver failure, emphasizing the necessity of direct administration using a scaffold. A fibrin gel scaffold was employed for ADSCs (gelADSC) to assess their therapeutic impact on liver regeneration in both in vitro and in vivo settings. Experiments were conducted on C57BL/6 mice with normal livers and those with chronic hepatitis. We also explored the role of extracellular vesicles (EVs) secreted by ADSCs in conjunction with fibrin gel. GelADSC showed sustained release of hepatocyte growth factor, vascular endothelial growth factor, and stromal cell-derived factor 1 for at least 7 days in vitro. In vivo, gelADSC significantly enhanced postoperative liver regeneration by upregulating the cell cycle and fatty acid oxidation in both normal and chronically hepatitis-affected mice. The therapeutic effects of gelADSC were potentially favorable over those of intravenously administered ADSCs, especially in mice with chronic hepatitis. Increased EV secretion associated with fibrin gel use was significantly linked to enhanced liver regeneration post-surgery through the promotion of fatty acid oxidation. The findings underscore the enhanced therapeutic potential of gelADSC, particularly in the context of chronic hepatitis, possibly compared to intravenous administration.

To evaluate the clinical outcomes of intra-articular stromal vascular fraction (SVF) and adipose-derived mesenchymal stem cell (ASC) injections in patients with knee osteoarthritis through a meta-analysis of randomized clinical trials.

PubMed, Embase, the Cochrane Library, and Google Scholar were systematically searched to identify Level I studies that compared the clinical efficacy of SVF or ASC with that of other nonoperative treatments. Clinical scores measured 3, 6, and 12 months postinjection were standardized to pain and functional scales for meta-analysis based on minimal clinically important differences. Follow-up magnetic resonance imaging findings and safety-related data were also investigated.

Nine studies involving 671 patients were included. SVF demonstrated superior pain and function score improvements compared to saline or hyaluronic acid (HA) at 3, 6, and 12 months postinjection. However, SVF was inferior to corticosteroid at 3 months, showed no difference at 6 months, and was comparable or slightly superior at 12 months. ASC consistently showed better pain and function score improvements compared to saline and conservative treatment at all time points, with no significant differences observed compared to HA. High heterogeneity was noted in SVF function score results, requiring cautious interpretation. No serious adverse events related to SVF or ASC were reported, although complications associated with liposuction were observed.

SVF showed consistent superiority in pain and function scores compared to HA and saline but not corticosteroids, except for the 3-month function score. ASC improved pain and function scores compared to saline and conservative treatment but was not superior to HA. While SVF and ASC significantly improved clinical scores, the potential complications from liposuction limit their ability to replace existing minimally invasive treatments for knee osteoarthritis.

Level I, meta-analyses of randomized controlled trials.

A histological comparison of lipofilling and hyaluronic acid filler injection was performed in rats. Studies at the histological level showed that, compared with hyaluronic acid filler injection, autologous fat grafting led to a more uniform distribution of adipose tissue at 30 days after treatment and a decrease in the area of sebaceous glands. Compared with lipofilling, the hyaluronic acid filler facilitated an increase in epidermis thickness because the granular layer and dermis grew thicker in addition to the filler injected into the subcutaneous space.

Spinal fusion surgery remains a significant challenge due to limitations in current bone graft materials, particularly in terms of bioactivity, integration, and safety. This study presents an innovative approach using an injectable hydroxyapatite/β-tricalcium phosphate (HA/β-TCP) hydrogel combined with stromal vascular fraction (SVF) and low-dose recombinant human BMP-2 (rhBMP-2) to enhance osteodifferentiation and angiogenesis. Through a series of in vitro studies and preclinical models involving rats and minipigs, we demonstrated that the hydrogel system enables the sustained release of rhBMP-2, resulting in significantly improved bone density and integration, alongside reduced inflammatory responses. The combination of rhBMP-2 and SVF in this injectable formulation yielded superior spinal fusion outcomes, with enhanced mechanical properties and increased bone mass in both small and large animal models. These findings suggest that this strategy offers a promising and safer alternative for spinal fusion, with strong potential for clinical application.

Stromal Vascular Fraction (SVF) has gained significant attention in clinical applications due to its regenerative and anti-inflammatory properties. Initially identified decades ago, SVF is derived from adipose tissue and has been increasingly utilized in a variety of therapeutic settings. The isolation and processing protocols for SVF have evolved substantially, particularly after its classification as an Advanced Therapy Medicinal Product (ATMP), which mandates adherence to Good Manufacturing Practices to ensure sterility and product quality. Despite the progress, few studies over the last decade have focused on the standardization of SVF processing. Recent advances, driven by the potential of SVF and its derived products such as Adipose-derived Stem Cells, have prompted the development of improved isolation strategies aimed at enhancing their therapeutic and regenerative efficacy. Notable progress includes the advent of automated processing systems, which reduce technical errors, minimize variability, and improve reproducibility across laboratories. These developments, along with the establishment of more precise protocols and guidelines, have enhanced the consistency and clinical applicability of SVF-based therapies. This review discusses the key aspects of SVF isolation and processing, highlighting the efforts to standardize the procedure and ensure the reliability of SVF products for clinical use.

A catalytic ROS-scavenging hydrogel (HGel) was developed to enhance the growth factor secretion and the therapeutic efficacy of human adipose-derived stem cells (hADSCs) in inflammatory environments. The HGel is composed of heparin and hyaluronic acid, further functionalized with hemin to endow superoxide dismutase and catalase activities. The functionalization of hemin enables the HGel to effectively scavenge ROS (superoxide and H2O2), thereby protecting encapsulated hADSCs from oxidative stress and maintaining their metabolic activities. As a result, the HGel enhanced growth factor secretion of hADSCs in inflammatory conditions compared to non-functionalized, bare heparin/hyaluronic acid hydrogel (Gel). The therapeutic efficacy of the hADSC-encapsulated HGel (C/HGel) was evaluated in a diabetic wound model. The C/HGel significantly accelerated wound closure, reduced ROS levels, mitigated inflammation, and promoted angiogenesis compared to the hADSC-encapsulated Gel (C/Gel) as well as the HGel itself. The HGel has the potential to be utilized as an excellent cell carrier for stem cell therapy in various inflammatory diseases. Overall, this study demonstrated a strategy of enhancing growth factor secretion from stem cells using catalytic antioxidant hydrogels for superior regenerative effects in cell therapy.

Micro-fragmented adipose tissue is emerging as a promising option for the treatment of various diseases including knee osteoarthritis (OA), though clinical trials are often limited by short follow-up periods. Our aim was to evaluate the safety and clinical outcomes of an arthroscopic debridement followed by a single injection of micro-fragmented adipose tissue in patients affected by knee OA.

From 2016 to 2020, patients affected by knee OA were enroled. Micro-fragmented adipose tissue was obtained through the Lipogems® kit and intraarticularly injected after an arthroscopic debridement. Visual analogue scale for pain, Tegner score, Knee Injury and Osteoarthritis Outcome score subscales variations were assessed from baseline to 3, 6, 12, 24 and 48 months of follow-up.

Forty-one patients were evaluated up to 6 months of follow-up, 39 patients up to 24 months of follow-up and 38 patients up to 48 months of follow-up. Three underwent knee replacement surgery during the time of the study. All the clinical scores analyzed achieved statistically significant changes up to the last follow-up.

A single intra-articular knee injection of micro-fragmented adipose tissue following arthroscopic debridement is able to provide significant clinical benefits in patients affected by knee OA up to 4 years of follow-up.The present clinical study was registered on clinicaltrials.gov (no. NCT06545266).

Level IV case series.

Perianal fistulas have posed a medical and surgical problem since ancient times. The plethora of surgical operations described nowadays for anal fistula treatment is real proof that there is no ideal therapeutic procedure. The cornerstone of all approaches is the equilibrium between the definitive treatment of the fistula with the maintenance of the anal continence mechanism, i.e., anal sphincters. Especially complex anal fistulas (multiple tracts, high transphincteric fistulas, rectovaginal and Crohn disease-associated anal fistulas) are difficult to deal with to preserve this therapeutic balance. Contemporary experimental procedures include the use of autologous biological products such as platelet-rich plasma (PRP) and mesenchymal stem cells (MSCs), either in their "raw" matrix (stromal vascular fraction, SVF) or after isolation and cultivation before delivered to the patient. Herein, we present a new experimental procedure that we implemented for four patients with perianal fistulas, which is safe and effective, easily reproduced, and cheap. It is a one-stage procedure that requires only simple means and could serve as a first-line approach in complex anal fistulas. In this article, we will present four indicative cases treated with this method, using different syringes for various patient conditions, while analyzing the corresponding clinical and imaging results.

Diabetic foot ulcers (DFUs) cause prominent morbidity and mortality. Adipose mesenchymal stem cell (ASC)-derived extracellular vesicles (EVs) show property in facilitating diabetic wound healing, and we explored their role in DFU rats.

ASCs were cultured in vitro, passaged and then identified by flow cytometry and induction of osteogenic/adipogenic differentiation. ASC-EVs were extracted and identified. DFU rat model was treated with ASC-EVs. High glucose (HG)-induced rat dermal fibroblasts were treated with ASC-EVs or 3-MA and sh-PINK1 plasmid in vitro. Wound healing was observed. Histological changes, inflammatory cytokines (TNF-α, IL-1β), and α-SMA and p21 double-positive cell level were assessed by HE staining, ELISA, and immunofluorescence. Mitochondrial membrane potential (MMP), cell viability and senescence, and ROS production in cells were assessed by fluorescence dye JC-1, CCK-8, SA-β-gal staining, and ROS kit. p21, LC3II/I, p62, PINK1 and parkin protein levels were determined by Western blot.

DFU rats had slow wound healing and elevated levels of IL-1β, TNF-α, α-SMA and p21 double-positive cells, and SA-β-gal, while HG-induced cells had weakened viability, elevated ROS, SA-β-gal, p21 and p62 protein levels, and decreased LC3II/I, PINK1 and parkin protein levels and MMP, which were reversed by ASC-EVs. HG inhibited mitophagy by suppressing the PINK1/parkin pathway to accelerate dermal fibroblast senescence. The PINK1/parkin pathway inhibition partly mitigated the effect of ASC-EVs. ASC-EVs promoted mitophagy by activating the PINK1/parkin pathway in vivo.

ASC-EVs mediated mitophagy by activating the PINK1/parkin pathway, thereby impeding HG-induced rat dermal fibroblast senescence and promoting wound healing in DFU rats.

Hydrogels are commonly used as carriers for cell delivery due to their similarities to the extracellular matrix. A contraction-suppressed full-thickness wound model was used to evaluate the therapeutic potential of Pluronic F127 (PF127) hydrogel loaded with adipose-derived stromal vascular fraction (AdSVF), mesenchymal stem cells (AdMSC), and conditioned media (AdMSC-CM) for the repair of wounds in a rabbit model. The experimental study was conducted on forty-eight healthy adult New Zealand white rabbits randomly divided into eight groups with six animals each and treated with AdSVF, AdMSC, and AdMSC-CM as an injectable or topical preparation. The healing potential of different adipose-derived cell-based and cell-free therapeutics was evaluated based on percentage wound healing, period of epithelialization, epidermal thickness, scar evaluation, histopathology analysis, histochemical evaluation, immunohistochemistry (collagen type I), and hydroxyproline assay by comparing with the positive and negative control. Collagen density analysis using different staining methods, immunohistochemistry, and hydroxyproline assay consistently showed that delivering AdMSC and AdMSC-CM in PF127 hydrogel enhanced epithelialization, collagen production, and organization, contributing to improved tissue strength and quality. Even though allogeneic AdSVF was found to promote wound healing in rabbits, it has a lower potential than AdMSC and AdMSC-CM. The wound healing potential of AdMSC and AdMSC-CM was enhanced when loaded in PF127 hydrogel and applied topically. Even though wounds treated with AdMSC outperformed AdMSC-CM, a significant difference in the healing quality was not observed in most instances, indicating almost similar therapeutic potential. The findings indicate that the wound healing potential of AdMSC and AdMSC-CM was enhanced when loaded in PF127 hydrogel and applied topically. These treatments promoted collagen production, tissue organization, and epidermal regeneration, ultimately improving overall healing outcomes.

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.

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.

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.

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.

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.

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 .

Blue light (BL)-induced retinal injury has become a very common problem due to over exposure to blue light-emitting sources. This study aimed to investigate the possible ameliorating impact of stromal vascular fraction cells (SVFCs) on BL-induced retinal injury. Forty male albino rats were randomly allocated into four groups. The control group rats were kept in 12-h light/12-h dark. Rats of SVFC-control as the control group, but rats were intravenously injected once by SVFCs. Rats of both the BL-group and BL-SVFC group were exposed to BL for 2 weeks; then rats of the BL-SVFC group were intravenously injected once by SVFCs. Following the BL exposure, rats were kept for 8 weeks. Physical and physiological studies were performed; then retinal tissues were collected for biochemical and histological studies. The BL-group showed physical and physiological changes indicating affection of the visual function. Biochemical marker assessment showed a significant increase in MDA, TLR4 and MYD88 tissue levels with a significant decrease in TAC levels. Histological and ultrastructural assessment showed disruption of the normal histological architecture with retinal pigment epithelium, photoreceptors, and ganglion cell deterioration. A significant increase in NF-κB, caspase-3, and GFAP immunoreactivity was also detected. BL-SVFC group showed a significant improvement in physical, physiological, and biochemical parameters. Retinal tissues revealed amelioration of retinal structural and ultrastructural deterioration and a significant decrease in NF-κB and caspase-3 immunoreactivity with a significant increase in GFAP immunoreaction. This study concluded that SVFCs could ameliorate the BL-induced retinal injury through TLR-4/MYD-88/NF-κB signaling inhibition, regenerative, anti-oxidative, and anti-apoptotic effects.

Spatial transcriptomics (ST) technologies have advanced to enable transcriptome-wide gene expression analysis at submicron resolution over large areas. However, analysis of high-resolution ST is often challenged by complex tissue structure, where existing cell segmentation methods struggle due to the irregular cell sizes and shapes, and by the absence of segmentation-free methods scalable to whole-transcriptome analysis. Here we present FICTURE (Factor Inference of Cartographic Transcriptome at Ultra-high REsolution), a segmentation-free spatial factorization method that can handle transcriptome-wide data labeled with billions of submicron-resolution spatial coordinates and is compatible with both sequencing-based and imaging-based ST data. FICTURE uses the multilayered Dirichlet model for stochastic variational inference of pixel-level spatial factors, and is orders of magnitude more efficient than existing methods. FICTURE reveals the microscopic ST architecture for challenging tissues, such as vascular, fibrotic, muscular and lipid-laden areas in real data where previous methods failed. FICTURE's cross-platform generality, scalability and precision make it a powerful tool for exploring high-resolution ST.

Loss of terminal differentiation is a hallmark of cancer and offers a potential mechanism for differentiation therapy. Polycomb repressive complex 2 (PRC2) serves as the methyltransferase for K27 of histone H3 that is crucial in development. While PRC2 inhibitors show promise in treating various cancers, the underlying mechanisms remain incompletely understood. Here, we demonstrated that the inhibition or depletion of PRC2 enhanced adipocyte differentiation in malignant rhabdoid tumors and mesenchymal stem cells, through upregulation of peroxisome proliferator-activated receptor gamma (PPARG) and CEBPA. Mechanistically, PRC2 directly represses their transcription through H3K27 methylation, as both genes exhibit a bivalent state in mesenchymal stem cells. KO of PPARG compromised C/EBPα expression and impeded the PRC2 inhibitor-induced differentiation into adipocytes. Furthermore, the combination of the PPARγ agonist rosiglitazone and the PRC2 inhibitor MAK683 exhibited a higher inhibition on Ki67 positivity in tumor xenograft compared to MAK683 alone. High CEBPA, PLIN1, and FABP4 levels positively correlated with favorable prognosis in sarcoma patients in The Cancer Genome Atlas cohort. Together, these findings unveil an epigenetic regulatory mechanism for PPARG and highlight the essential role of PPARγ and C/EBPα in the adipocyte differentiation of malignant rhabdoid tumors and sarcomas with a potential clinical implication.

Skin healing is a complex and dynamic physiological process that follows mechanical alteration of the skin barrier. Under normal conditions, this complex process can be divided into at least three continuous and overlapping phases: an inflammatory reaction, a proliferative phase that leads to tissue reconstruction and a phase of tissue remodeling. Macrophages critically contribute to the physiological cascade for tissue repair. In fact, as the inflammatory phase progresses, macrophage gene expression gradually shifts from pro-inflammatory M1-like to pro-resolutive M2-like characteristics, which is critical for entry into the repair phase. A dysregulation in this macrophage' shift phenotype leads to the persistence of the inflammatory phase. Mesenchymal stromal cells and specifically the MSC-derived from adipose tissue (ADSCs) are more and more use to treat inflammatory diseases and several studies have demonstrated that ADSCs promote the wound healing thanks to their neoangiogenic, immunomodulant and regenerative properties. In several studies, ADSCs and macrophages have been injected directly into the wound bed, but the delivery of exogenous cells directly to the wound raise the problem of cell engraftment and preservation of pro-resolutive phenotype and viability of the cells. Complementary approaches have therefore been explored, such as the use of biomaterials enriched with therapeutic cell to improve cell survival and function. This review will present a background of the current scaffold models, using adipose derived stromal-cells and macrophage as therapeutic cells for wound healing, through a discussion on the potential impact for future applications in skin regeneration. According to the PRISMA statement, we resumed data from investigations reporting the use ADSCs and bioscaffolds and data from macrophages behavior with functional biomaterials in wound healing models. In the era of tissue engineering, functional biomaterials, that can maintain cell delivery and cellular viability, have had a profound impact on the development of dressings for the treatment of chronic wounds. Promising results have been showed in pre-clinical reports using ADSCs- and macrophages-based scaffolds to accelerate and to improve the quality of the cutaneous healing.

Adipose tissue was previously regarded as a dormant organ for lipid storage until the identification of adiponectin and leptin in the early 1990s. This revelation unveiled the dynamic endocrine function of adipose tissue, which has expanded further. Adipose tissue has emerged in recent decades as a multifunctional organ that plays a significant role in energy metabolism and homeostasis. Currently, it is evident that adipose tissue primarily performs its function by secreting a diverse array of signaling molecules known as adipokines. Apart from their pivotal function in energy expenditure and metabolism regulation, these adipokines exert significant influence over a multitude of biological processes, including but not limited to inflammation, thermoregulation, immune response, vascular function, and insulin sensitivity. Adipokines are pivotal in regulating numerous biological processes within adipose tissue and facilitating communication between adipose tissue and various organs, including the brain, gut, pancreas, endothelial cells, liver, muscle, and more. Dysregulated adipokines have been implicated in several metabolic diseases, like obesity and diabetes, as well as cardiovascular diseases. In this article, we attempted to describe the significance of adipokines in developing metabolic and cardiovascular diseases and highlight their role in the crosstalk between adipose tissues and other tissues and organs.

There is presently no disease-modifying therapy for Alzheimer's Disease (AD), which is the most prevalent cause of dementia.

This study aspires to estimate the efficacy and safety of cell-based treatments in AD.

Observing the Joanna Briggs Institute (JBI) methods and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, a systematic search was accomplished in PubMed, Medical Literature Analysis and Retrieval System Online (Medline, via Ovid), Embase; Cochrane, and Cumulative Index of Nursing and Allied Health Literature - CINAHL (via EBSCO) databases up to June 2023. The relevant clinical studies in which cell-based therapies were utilized to manage AD were included. The risk of bias was evaluated using the JBI checklists, based on the study designs.

Out of 1,014 screened records, a total of five studies with 70 individuals (including 59 patients receiving stem cells and 11 placebo controls) were included. In all these studies, despite the discrepancy in the origin of stem cells, cell density, and transplant site, safety goals were obtained. The intracerebroventricular injection of adipose-derived stromal vascular fraction (ADSVF) and umbilical cord-derived mesenchymal stem cells (UC-MSCs), the intravenous injection of Lomecel-B, and the bilateral hippocampi and right precuneus injection of UC-MSCs are not linked to any significant safety concerns, according to the five included studies. Studies also revealed improvements in biomarkers and clinical outcomes as a secondary outcome. Three studies had no control groups and there are concerns regarding the similarity of the groups in others. Also, there is considerable risk of bias regarding the outcome assessment scales.

Cell-based therapies are well tolerated by AD patients, which emphasizes the need for further, carefully planned randomized studies to reach evidence-based clinical recommendations in this respect.

A pharyngocutaneous fistula is one of the complications after laryngeal and pharyngeal surgery. It may also contribute to wound healing due to adipose tissue-derived stem cells and the growth factors in the stromal vascular fraction. The aim of this study was to investigate the effects of the adipose tissue-derived stromal vascular fraction on wound healing in the pharyngocutaneous fistula model induced in rats.

Approval was received from the Animal Experiments Local Ethics Committee before starting the study (29.01.2016-2016/09). Eleven male Sprague-Dawley rats weighing approximately 300 g were included in the study. The animals were randomly divided into the study and control groups so that each group would include five animals. An animal was assigned as a donor for the removal of omental adipose tissue. Among the animals in which the pharyngocutaneous fistula model was created under general anesthesia, 1 ml of the stromal vascular fraction was injected into the study group on postoperative day 1. In postoperative week 2, all the animals were sacrificed and examined histologically (epithelialization-cell infiltration - mucosal injury). IBM SPSS Statistics for Windows, version 15, was used in the analyses. A p-value <0.05 was considered significant.

Epithelialization was higher in the study group compared to the control group. However, no statistically significant difference was found between the two groups (p = 0.08). The cell infiltration was found to be statistically higher in the control group compared to the study group (p = 0.03). The mucosal injury was found to be significantly higher in the control group compared to the study group (p = 0.03). According to the Pearson correlation test, a negative correlation was found between epithelialization and cell infiltration and mucosal injury (p = 0.019 and p = 0.001). A positive correlation was found between cell infiltration and mucosal injury (p = 0.009).

It was shown that stromal vascular fraction had a positive effect on wound healing in the pharyngocutaneous fistula model. According to the data we have obtained, we think that it can be effective in the treatment of pharyngocutaneous fistulas after more extensive preclinical and clinical studies are carried out.

In regenerative medicine, the isolation of mesenchymal stromal cells (MSCs) from the adipose tissue's stromal vascular fraction (SVF) is a critical area of study. Our review meticulously examines the isolation process of MSCs, starting with the extraction of adipose tissue. The choice of liposuction technique, anatomical site, and immediate processing are essential to maintain cell functionality. We delve into the intricacies of enzymatic digestion, emphasizing the fine-tuning of enzyme concentrations to maximize cell yield while preventing harm. The review then outlines the filtration and centrifugation techniques necessary for isolating a purified SVF, alongside cell viability assessments like flow cytometry, which are vital for confirming the efficacy of the isolated MSCs. We discuss the advantages and drawbacks of using autologous vs allogeneic SVF sources, touching upon immunocompatibility and logistical considerations, as well as the variability inherent in donor-derived cells. Anesthesia choices, the selection between hypodermic needles vs liposuction cannulas, and the role of adipose tissue lysers in achieving cellular dissociation are evaluated for their impact on SVF isolation. Centrifugation protocols are also analyzed for their part in ensuring the integrity of the SVF. The necessity for standardized MSC isolation protocols is highlighted, promoting reproducibility and successful clinical application. We encourage ongoing research to deepen the understanding of MSC biology and therapeutic action, aiming to further the field of regenerative medicine. The review concludes with a call for rigorous research, interdisciplinary collaboration, and strict adherence to ethical and regulatory standards to safeguard patient safety and optimize treatment outcomes with MSCs.

Mesenchymal Stromal Cells (MSCs) offer tremendous potential for the treatment of various diseases and their healing properties have been explored in hundreds of clinical trials. These trails primarily focus on immunological and neurological disorders, as well as regenerative medicine. Adipose tissue is a rich source of mesenchymal stromal cells and methods to obtain and culture adipose-derived MSCs (AD-MSCs) have been well established. Promising results from pre-clinical testing of AD-MSCs activity prompted clinical trials that further led to the approval of AD-MSCs for the treatment of complex perianal fistulas in Crohn's disease and subcutaneous tissue defects. However, AD-MSC heterogeneity along with various manufacturing protocols or different strategies to boost their activity create the need for standardized quality control procedures and safety assessment of the intended cell product. High-resolution transcriptomic methods have been recently gaining attention, as they deliver insight into gene expression profiles of individual cells, helping to deconstruct cellular hierarchy and differentiation trajectories, and to understand cell-cell interactions within tissues. This article presents a comprehensive overview of completed clinical trials evaluating the safety and efficacy of AD-MSC treatment, together with current single-cell studies of human AD-MSC. Furthermore, our work emphasizes the increasing significance of single-cell research in elucidating the mechanisms of cellular action and predicting their therapeutic effects.

Full-thickness skin grafts are widely used in plastic and reconstructive surgery. The main limitation of skin grafting is the poor textural durability and associated contracture, which often needs further corrective surgery. Excessive inflammation is the main reason for skin graft contractions, which involve overactivation of myofibroblasts. These problems have prompted the development of new therapeutic approaches, including macrophage polarization modulation and stem cell-based therapies. Currently, adipose-derived stem cells (ASCs) have shown promise in promoting skin grafts survival and regulating macrophage phenotypes. However, the roles of ASCs on macrophages in decreasing skin grafts contraction remain unknown.

Rat adipose-derived stem cells (rASCs) were isolated from rat inguinal adipose tissues. Full-thickness skin graft model was constructed on male rats divided into control group and rASCs treatment group. Skin graft was assessed for concentration, elasticity modulus and stiffness. Rat bone marrow-derived macrophages (rBMDMs) were isolated from rat femurs, and subsequent RT-qPCR and coculture assays were carried out to explore the cellular mechanisms. Immunohistochemical and immunofluorescence staining were used to verify mechanisms in vivo.

In vivo results showed that after injection of ASCs, improved texture, increased survival and inhibited contraction of skin grafts were seen. Vascularization was also improved as illustrated by laser perfusion image and vascular endothelial growth factor (VEGF) concentration. Histological analysis revealed that ASCs injection significantly reduced expression of pro-inflammatory cytokines (TNF-a, IL-1β) and increased expression of anti-inflammatory (IL-10) and pro-healing cytokines (IGF-1). At cellular level, after co-culturing with rASCs, rat bone marrow derived macrophages (rBMDMs) favored M2 polarization even under inflammatory stimulus.

ASCs treatment enhanced vascularization via angiogenic cytokines secretion and alleviated inflammatory environment in skin grafts by driving M2 macrophages polarization, which improved survival and decreased skin grafts contraction. Our work showed that ASCs transplantation can be harnessed to enhance therapeutic efficacy of skin grafting in cutaneous defects treatment.

Cartilage defects are a common pathology in active people and affect quality of life. A common treatment option is treatment with minced cartilage (MC). As conservative therapy has a limited effect, surgical treatments vary in terms of procedure and results. A modified technique for autologous cartilage repair is presented here.

MC was modified by adding a synovial sealant. This improves the stability of the graft, allowing the cartilage to proliferate. The synovial tissue has the potential to stimulate the implanted cartilage, which promotes healing and regeneration. The clinical and functional results of the modified technique were examined in a retrospective case series.

The technique has proven to be reproducible for retropatellar cartilage defects and is both efficient and cost effective. MC with synovial sealing was performed in ten patients with retropatellar cartilage damage. In the conducted cases serious, 10 patients were available for follow-up after 18 ± 3 months. Patients showed good clinical results in terms of pain (VAS = 1.9, KOOS Pain = 89.7), symptoms (KOOS Symptoms = 83.6), and daily activity (KOOS Activity = 96.6).

The procedure combines the advantages of autologous cartilage repair with a one-stage surgical approach. It utilizes the regenerative potential of synovial tissue while providing improved mechanical stability. This technique offers a cost-effective, autologous solution for full-thickness cartilage defects, and shows promising clinical results in the medium term.

This study aims to investigate the potential of stromal vascular fraction (SVF) for peripheral nerve regeneration.

A scoping review of Scopus and PubMed databases was conducted. Inclusion criteria were human or animal studies exploring the use of SVF for peripheral nerve regeneration. Studies were categorized by assessed outcomes: pain assessment, neural integrity, muscle recovery, and functional recovery. Level of evidence and study quality were assessed.

Nine studies met the inclusion criteria. SVF injection in humans with trigeminal neuropathic pain reduced pain scores from 7.5 ± 1.58 to 4.3 ± 3.28. SVF injection improved sensation in humans with leprosy neuropathy. Repairing transected rat sciatic nerves with SVF-coated nerve autografts improved wet muscle weight ratios (0.65 ± 0.11 vs 0.55 ± 0.06) and sciatic functional index (SFI) scores (-68.2 ± 9.2 vs -72.5 ± 8.9). Repairing transected rat sciatic nerves with SVF-coated conduits increased the ratio of gastrocnemius muscle weights (RGMW) (7-10% improvement), myelinated fibers (1,605 ± 806.2 vs 543.6 ± 478.66), and myelin thickness (5-20% increase). Repairing transected rat facial nerves with SVF-coated conduits improved whisker motion (9.22° ± 0.65° vs 1.90° ± 0.84°) and myelin thickness (0.57 μm ± 0.17 vs 0.45 μm ± 0.14 μm). Repairing transected rat sciatic nerves with SVF-coated nerve allografts improved RGMW (85 vs 50%), SFI scores (-20 to -10 vs -40 to -30), and Basso, Beatie, and Bresnahan locomotor scores (18 vs 15). All metrics mentioned above were statistically significant. The human studies were level 4 evidence due to being case series, while animal studies were the lowest level of evidence.

Despite initial promising results, the low-level evidence from the included studies warrants further investigation.

Numerous studies have proposed the utilization of stromal vascular fraction (SVF), adipose-derived stem cells (ADSCs), and platelet products as auxiliary grafting techniques to improve the survival rate of fat grafts. This study aimed to evaluate the efficacy and safety of various fat grafting methods since 2010 through a network meta-analysis, aiming to identify the most effective technique for fat grafting.

Clinic trials on assisted fat grafting were searched from Pubmed, Embase, Web of Science, and the Cochrane Library, spanning the period from January 1, 2010 to March 2024. The risk of bias in the included trials was meticulously assessed using the Cochrane risk of bias tool. The survival rate of fat grafts served as the primary evaluation metric for effectiveness, while complications were employed as the indicator for safety.

The study incorporated 31 clinic trials, involving a total of 1656 patients. The findings indicated that the survival rate with assisted fat grafting significantly surpassed that of simple fat grafting (SUCRA, 10.43%). Notably, ADSC-assisted fat grafting exhibited the highest survival rate (SUCRA, 82.17%), followed by Salvia miltiorrhiza (SM)-assisted fat grafting (SUCRA, 69.76%). In terms of safety, the most prevalent complications associated with fat grafting were fat sclerosis and fat necrosis. Adc-assisted fat grafting was correlated with the lowest incidence of complications (SUCRA, 41.00%), followed by simple fat grafting (SUCRA, 40.99%). However, PRP-assisted (SUCRA, 52.86%) and SVF-assisted fat grafting (SUCRA, 65.14%) showed higher complication rates.

Various methods of assisted fat grafting can significantly enhance the survival rate, but they often fail to effectively mitigate the incidence of complications. Compared to other methods, adipose mesenchymal stem cells-assisted fat grafting consistently yielded a higher survival rate of grafts and fewer complications. Consequently, this approach represents a relatively effective method for assisting in fat grafting at present.

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 .

Regenerative therapies such as fat grafting and Platelet Rich Plasma (PRP) have emerged as new options to tackle burn-related injuries and their long-term sequelae. Fat grafting is able to promote wound healing by regulating the inflammatory response, stimulating angiogenesis, favoring the remodeling of the extracellular matrix, and enhancing scar appearance. PRP can enhance wound healing by accelerating stages including hemostasis and re-epithelization. It can improve scar quality and complement fat grafting procedures. Their cost-effectiveness, minimal invasiveness, and promising results observed in the literature have made these tools as therapeutic candidates. The current evidence on fat grafting and PRP in acute and reconstructive burns is described and discussed in this study.

Autologous fat (AF) grafting is widely used in plastic surgery and is generally considered a safe and effective procedure. A combined approach utilizing vibration amplification of sound energy at resonance (VASER) to prepare AF grafts with a 4-layer fat grafting technique was explored in this study.

To offer a customized solution that accommodates individual anatomical differences.

This retrospective, cross-sectional case series involved 40 breasts from 20 female patients who underwent primary augmentation-mastopexy. After removing excess breast tissue and exposing the pedicle, lateral pillars, and pectoral muscle, the 4-layer fat grafting was performed as follows: 150 mL of AF under the pectoral muscle directed toward the medial and central zones; 100 mL into the pectoral muscle toward these zones; 50 mL under the pectoral fascia, moving retrograde from cephalic to caudal portions at a 30° to 45° cannula angle. After closing the epithelial and subepithelial incisions, an additional 100 to 150 mL of AF was injected under the subcutaneous layer around the breast, depending on each patient's contour and breast shape. Patients were monitored for 2 years with MRI scans to assess breast volume, anatomy, and fat graft survival.

The average follow-up was 26 ± 2.81 months. MRI evaluations indicated an efficient survival rate of the fat grafts. None of the patients experienced minor or major complications.

The 4-layer AF grafting technique appears to be a safe and effective procedure for customized breast sculpting in augmentation-mastopexy surgery, with a high rate of fat graft sustainability and survival.

Bone regeneration involves multiple factors such as tissue interactions, an inflammatory response, and vessel formation. In the event of diseases, old age, lifestyle, or trauma, bone regeneration can be impaired which could result in a prolonged healing duration or requiring an external intervention for repair. Currently, bone grafts hold the golden standard for bone regeneration. However, several limitations hinder its clinical applications, e.g., donor site morbidity, an insufficient tissue volume, and uncertain post-operative outcomes. Bone tissue engineering, involving stem cells seeded onto scaffolds, has thus been a promising treatment alternative for bone regeneration. Adipose-derived mesenchymal stem cells (AD-MSCs) are known to hold therapeutic value for the treatment of various clinical conditions and have displayed feasibility and significant effectiveness due to their ease of isolation, non-invasive, abundance in quantity, and osteogenic capacity. Notably, in vitro studies showed AD-MSCs holding a high proliferation capacity, multi-differentiation potential through the release of a variety of factors, and extracellular vesicles, allowing them to repair damaged tissues. In vivo and clinical studies showed AD-MSCs favoring better vascularization and the integration of the scaffolds, while the presence of scaffolds has enhanced the osteogenesis potential of AD-MSCs, thus yielding optimal bone formation outcomes. Effective bone regeneration requires the interplay of both AD-MSCs and scaffolds (material, pore size) to improve the osteogenic and vasculogenic capacity. This review presents the advances and applications of AD-MSCs for bone regeneration and bone tissue engineering, focusing on the in vitro, in vivo, and clinical studies involving AD-MSCs for bone tissue engineering.

Adipose-derived stem cells (ADSCs) are a subset of mesenchymal stem cells (MSCs) isolated from adipose tissue. They possess remarkable properties, including multipotency, self-renewal, and easy clinical availability. ADSCs are also capable of promoting tissue regeneration through the secretion of various cytokines, factors, and extracellular vesicles (EVs). ADSC-derived EVs (ADSC-EVs) act as intercellular signaling mediators that encapsulate a range of biomolecules. These EVs have been found to mediate the therapeutic activities of donor cells by promoting the proliferation and migration of effector cells, facilitating angiogenesis, modulating immunity, and performing other specific functions in different tissues. Compared to the donor cells themselves, ADSC-EVs offer advantages such as fewer safety concerns and more convenient transportation and storage for clinical application. As a result, these EVs have received significant attention as cell-free therapeutic agents with potential future application in regenerative medicine. In this review, we focus on recent research progress regarding regenerative medical use of ADSC-EVs across various medical conditions, including wound healing, chronic limb ischemia, angiogenesis, myocardial infarction, diabetic nephropathy, fat graft survival, bone regeneration, cartilage regeneration, tendinopathy and tendon healing, peripheral nerve regeneration, and acute lung injury, among others. We also discuss the underlying mechanisms responsible for inducing these therapeutic effects. We believe that deciphering the biological properties, therapeutic effects, and underlying mechanisms associated with ADSC-EVs will provide a foundation for developing a novel therapeutic approach in regenerative medicine.

Adipose-derived stem cells (ADSCs) are widely used in wound care because they release a variety of cytokines. However, the molecular mechanism of paracrine action remains unclear. It has been reported that basic fibroblast growth factor (bFGF) enhances the therapeutic potential of ADSCs. In this study, we searched for cytokines whose release from ADSCs is enhanced by bFGF stimulation.

Quantitative RT-PCR and ELISA analyses revealed that bFGF upregulates CXCL-1 and IL-8 mRNA synthesis and secretion from ADSCs. Both cytokines showed the ability to promote important processes for wound healing, including tube formation of vascular and lymphatic endothelial cells and cell migration of fibroblasts in vitro.

These results suggest that bFGF stimulation increases the secretion of CXCL-1 and IL-8 from ADSCs and that these cytokines may promote angiogenesis, lymphangiogenesis, and cell migration, leading to enhanced efficiency of wound healing.

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.

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.

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.