Search Results (230)

Human intraperitoneal omental adipose tissue, part of the visceral adipose depots, surrounds the abdominal organs and has functions distinct from the subcutaneous adipose depots. In the clinical setting, it is observed that the omentum is beneficial to combat internal sources of inflammation, oxidative stress, and injury-related stress. However, the molecular mechanisms involved in these functions are not fully understood. We previously demonstrated that adipose stem cells derived from human omental adipose tissue (om-hASCs) secrete exosomes (exos). We and others have extensively evaluated the subcutaneous adipose depot-derived exosomes; however, the role of adipose stem cells derived from the human omental depot (om-hASCs) remains less known. In this study, we postulated that exosomes from om-hASCs (om-hASCexos) drive the repair ability of the omentum to heal organs after internal injury and insults. First, we characterized the om-hASCexos using a proteomic analysis which identified the distinct cargo. Using in vitro injury models, we show that om-hASCexos significantly improve cell migration and proliferation, while decreasing oxidative stress and inflammation. To study acute in vivo healing, a rat wound model was evaluated. Om-hASCexos significantly improved the healing rate of injuries. RNAseq revealed that om-hASCexo treatment acts upon pathways associated with lipid and fatty acid metabolism, apoptosis, immune response, and cell differentiation. The pathway analysis indicated that om-hASCexos significantly regulate the expression of Clec5a and Trem1 in the immune response pathway. Overall, we demonstrate the singular properties of om-hASCexos that are distinct from other sources of hASC. Thus, this study provides an understanding of the unique ability of the omental adipose depot to combat internal injuries. Full article

Fascia, once considered a passive connective covering, is now recognized as a mechanosensitive tissue and stem cell niche with roles in regeneration, ECM remodeling, and immune–vascular regulation. The aim of this review was to synthetize evidence of fascia-derived progenitors and their mechanobiological functions across in vitro, preclinical and clinical domains. A systematic search of PubMed, Scopus and Web of Science (up to August 2025) was performed in accordance with PRIMS guidelines. Eligible studies addressed fascia in relation to stem/progenitor cells and regenerative outcomes. Risk of bias was assessed with OHAT criteria for in vitro studies, SYRCLE for animal studies and ROBINS-I for clinical studies. Of 648 records identified, 34 studies were included, encompassing 17 in vitro, 17 animal and 4 clinical investigations, with overlap across domains, and 3 reviews. In vitro, fascia-derived stem cells (FDSCs), FAPs and ASCs were shown to remodel ECM, promote angiogenesis and respond to mechanical cues. Animal models revealed collective fibroblast migration as ECM patches, regulated by N-cadherin, Connexin43 and p120-catenin, while CD201+ progenitors directed scar formation. Clinical studies, though few, reported improved outcomes with subfascial PRP injections and adipofascial flaps. Fascia appears as an active mechanobiological hub and stem cell reservoir that may influence tissue repair and fibrosis, although current evidence, particularly from clinical studies, remains preliminary. Despite promising insights, evidence is limited by methodological heterogeneity, emphasizing the need for mechanistic human studies and well-powered clinical trials. Full article

Mesenchymal stem cells (MSCs) spontaneously assemble into three-dimensional (3D) spheroids under matrix-deficient conditions such as the synovial cavity, although their functional significance has yet to be fully elucidated. In this study, we used concave microwell cultures to promote the spontaneous aggregation of adipose-derived MSCs (ASCs) from OA patients, thereby mimicking the intra-articular microenvironment. We analyzed the paracrine factors of ASC aggregates and compared it with that of conventional 2D monolayer cultures. Notably, 3D aggregation significantly increased the secretion of HGF and VEGF, whereas FGF2 levels remained relatively unchanged. These results indicate that the structural characteristics of ASC aggregates enhance the secretion of key paracrine factors involved in angiogenesis and tissue repair. To functionally evaluate the biological relevance of the secreted factors, conditioned media (CM) from ASC aggregates were applied to human articular chondrocytes. The CM significantly promoted chondrocyte proliferation, an effect that was abolished by the addition of HGF-neutralizing antibodies, thereby highlighting HGF as a central mediator of the regenerative response. Additionally, we further explored whether extracellular factors could modulate growth factor expression such as HGF. In this context, we investigated the impact of low-concentration hyaluronic acid (HA), a key synovial component widely used in OA treatment. Co-treatment with HA not only amplified the expression and secretion of HGF, VEGF, and FGF2, but also promoted ASC proliferation. ASCs forming functional aggregates may exert regenerative effects as active paracrine modulators, and the addition of low-dose hyaluronic acid is expected to further enhance this function, offering a promising strategy for MSC-based osteoarthritis therapy. Full article

Adipose-derived mesenchymal stem cells (ASCs) have great potential in regenerative medicine due to their abundance and innate multi-lineage differentiation potential. However, the therapeutic efficacy of ASCs is often compromised by poor microenvironmental conditions in the damaged tissues after transplantation. In this study, we generated and assessed genetically modified ASCs that expressed granulocyte chemotactic protein-2 (GCP-2) and platelet-derived growth factor-β (PDGF-β). The results revealed that three-dimensional (3D)-cultured ASCs overexpressing GCP-2 and PDGF-β (3D-A/GP) yielded a significant increase in proangiogenic gene expression, cell migration, and endothelial tube formation in vitro. Moreover, the Matrigel plug assay revealed that 3D-A/GP formed functional blood vessels, and 3D-A/GP injection in a hind limb ischemia (HLI) model revealed higher blood flow recovery, limb salvage, and capillary density and lower apoptosis in mice, compared to the controls. Notably, 3D-A/GP exhibited differentiation into endothelial-like cells and upregulated expression of angiogenic factors in ischemic limb tissue. Our results highlight the value of using a combination of genetic engineering and 3D culture systems to improve the therapeutic effect of ASCs in terms of angiogenesis-dependent tissue repair. The dual modulation of GCP-2 and PDGF-β, in combination with 3D culture, presents a new and synergistic opportunity to maximize the use of ASC-based therapies for ischemic diseases and other regenerative medicine applications. Full article

Aims: Diabetes mellitus (DM) increases cardiovascular risk by inducing atherosclerotic plaque instability. StemBell therapy (i.e., adipose tissue-derived stem cells (ASCs) coupled to ultrasound-activated microbubbles) previously improved plaque stability in non-DM ApoE^−/− mice. Here, we investigated the effect of StemBell therapy on atherosclerotic plaque characteristics in a streptozotocin-induced DM mouse model. Methods: DM was induced in male C57BL/6 ApoE^−/− mice (n = 18) via intraperitoneal streptozotocin (STZ) injection (0.05 mg/g bodyweight) for 5 consecutive days. Eight weeks after the first STZ injection, the mice received either 5 × 10⁵ StemBells or vehicle intravenously. Due to unexpected mortality, the experiment was halted and restarted in week 9 with a final reduced dose of 1.25 × 10⁵ StemBells to avoid complications. The effect of StemBell therapy on plaque characteristics was determined 4 weeks post-treatment in five vehicle-treated and five StemBell-treated mice via (immuno)histochemical analyses. Furthermore, plasma monocyte subsets within 3 days pre- and 3 days post-treatment, and 3 weeks post-treatment, were studied via flow cytometry. Results: StemBell therapy did not significantly affect atherosclerotic plaque size or intra-plaque inflammation. StemBell-treated mice had less intra-plaque Ly6G+ neutrophils (0.4 ± 0.5%) and intra-plaque Mac3+ pan-macrophages (17.7 ± 3.4%), but more CD163+ anti-inflammatory M2 macrophages (p = 0.5) compared to vehicle-treated mice, although this was non-significant. Conclusions: StemBell therapy did not significantly affect atherosclerotic plaque size or intra-plaque inflammation in a streptozotocin-induced DM mouse model. Future research is essential to explore the potential and limitations of StemBell therapy in DM-related atherosclerosis. The higher mortality of StemBell therapy in diabetic mice compared to the previous non-diabetic mice also warrants further investigation. Full article

Human adipose-derived stem cells (hASCs) are widely used in regenerative medicine due to their accessibility and high proliferative capacity. Platelet lysate (PL) has recently emerged as a promising alternative to fetal bovine serum (FBS), offering superior cell expansion potential; however, the molecular basis for its efficacy remains insufficiently elucidated. In this study, we performed RNA sequencing to compare hASCs cultured with PL or FBS, revealing a significant upregulation of genes related to stress response and cell proliferation under PL conditions. These findings were validated by RT–qPCR and supported by functional assays demonstrating enhanced cellular resilience to oxidative and genotoxic stress, reduced doxorubicin-induced senescence, and improved antiapoptotic properties. In a murine wound model, PL-treated wounds showed accelerated healing, characterized by thicker dermis-like tissue formation and increased angiogenesis. Immunohistochemical analysis further revealed elevated expression of chk1, a DNA damage response kinase encoded by CHEK1, which plays a central role in maintaining genomic integrity during stress-induced repair. Collectively, these results highlight PL not only as a viable substitute for FBS in hASC expansion but also as a bioactive supplement that enhances regenerative efficacy by promoting proliferation, stress resistance, and antiaging functions. Full article

The impact of donor age on Adipose-derived mesenchymal stem cell (ASC) functionality and safety remains insufficiently characterized, particularly in equine models. This study investigates the influence of age on ASCs proliferation dynamics and the expression of tumorigenic and apoptosis-related markers. Equine ASCs were isolated from juvenile (<5 years), middle-aged (5–15 years), and geriatric (>15 years) horses and assayed across multiple passages. The relative mRNA expressions of pluripotency (Oct4), tumorigenic (CA9), and apoptosis-related (Bax and Bcl 2) markers were evaluated. The Gompertz growth model, population doubling time (PDT), and tissue non-specific ALP activity also followed. The expression of pluripotency and tumorigenic markers showed passage-dependent up-regulation, raising concerns about prolonged culture expansion. Apoptotic regulation displayed a shift with aging, as evidenced by alterations in the Bax/Bcl2 ratio, suggesting compromised cell survival in older ASCs. An age-associated decline in proliferation rates was established, as evidenced by declining alkaline phosphatase (ALP) activity. These findings underscore the necessity for stringent age-based selection criteria in equine stem cell therapies and the challenges associated with using autologous stem cells for regenerative therapies in aged horses. Future research should focus on molecular interventions to mitigate age-related functional decline, ensuring the safety and efficacy of ASCs-based regenerative medicine in equine practice. Full article

Soft tissue reconstruction remains a challenge in clinical practice, particularly for restoring substantial volume loss due to surgical resections or contour deformities. Current methods, such as autologous fat transplantation, have limitations, including donor site morbidity and insufficient tissue availability, necessitating an innovative approach. This study characterizes alloClae, a minimally manipulated human-derived adipose allograft prepared using a detergent-based protocol to reduce DNA content while preserving adipose tissue structure. Proteomic analysis revealed that alloClae retains key native proteins critical for graft integration with the host and stability, with key extracellular matrix (ECM) components, collagens, elastins, and laminin, which are more concentrated as a result of the detergent-based protocol. Biocompatibility of alloClae was assessed in vitro using cytotoxicity and cell viability assays in fibroblast cultures, revealing no adverse effects on cell viability, membrane integrity, or oxidative stress. Additionally, in vitro studies with adipose-derived stem cells (ASCs) demonstrated attachment and differentiation, with lipid droplet accumulation observed by day 14, indicating support for adipogenesis. A 6-month longitudinal study in athymic mice showed stable graft retention, host cell infiltration, and formation of new adipocytes and vasculature within alloClae by 3 months. The findings highlight alloClae’s ability to support host-driven adipogenesis and angiogenesis while maintaining graft stability throughout the study period. It presents a promising alternative to the existing graft materials, offering a clinically translatable solution for soft tissue reconstruction. Full article

Diabetic foot ulcers (DFU) represent a major complication of diabetes mellitus, affecting millions of patients worldwide and leading to high morbidity and amputation risks. The impaired healing process in DFU is driven by vascular insufficiency, neuropathy, chronic inflammation, and infections. Conventional treatments, including blood sugar control, wound debridement, and standard dressings, have shown limited efficacy in achieving complete healing. Recent advancements have introduced novel therapeutic approaches such as stem cell therapy, exosome-based treatments, and bioengineered scaffolds to accelerate wound healing and tissue regeneration. Mesenchymal stem cells (MSCs), particularly adipose-derived stem cells (ASCs), exhibit anti-inflammatory, pro-angiogenic, and immunomodulatory properties, enhancing wound repair. Additionally, exosomes derived from ASCs have demonstrated the ability to promote fibroblast proliferation, regulate inflammation, and stimulate angiogenesis. The integration of bioengineered scaffolds, including hydrogels, hyaluronic acid (HA), or micro-fragmented adipose tissue (MFAT), offers improved drug delivery mechanisms and a controlled healing environment. These scaffolds have been successfully utilized to deliver stem cells, growth factors, antioxidants, anti-glycation end products, anti-inflammatory and anti-diabetic drugs, or antimicrobial agents, further improving DFU outcomes. This review highlights the potential of combining novel 3D scaffolds with anti-diabetic drugs to enhance DFU treatment, reduce amputation rates, and improve patients’ quality of life. While promising, further clinical research is required to validate these emerging therapies and optimize their clinical application. Full article

Prolonged breastfeeding (BF), as opposed to artificial infant formula feeding (FF), has been shown to prevent the development of obesity later in life. The aim of our narrative review is to investigate the missing molecular link between postnatal protein overfeeding—often referred to as the “early protein hypothesis”—and the subsequent transcriptional and epigenetic changes that accelerate the expansion of adipocyte stem cells (ASCs) in the adipose vascular niche during postnatal white adipose tissue (WAT) development. To achieve this, we conducted a search on the Web of Science, Google Scholar, and PubMed databases from 2000 to 2025 and reviewed 750 papers. Our findings revealed that the overactivation of mechanistic target of rapamycin complex 1 (mTORC1) and S6 kinase 1 (S6K1), which inhibits wingless (Wnt) signaling due to protein overfeeding, serves as the primary pathway promoting ASC commitment and increasing preadipocyte numbers. Moreover, excessive protein intake, combined with the upregulation of the fat mass and obesity-associated gene (FTO) and a deficiency of breast milk-derived microRNAs from lactation, disrupts the proper regulation of FTO and Wnt pathway components. This disruption enhances ASC expansion in WAT while inhibiting brown adipose tissue development. While BF has been shown to have protective effects against obesity, the postnatal transcriptional and epigenetic changes induced by excessive protein intake from FF may predispose infants to early and excessive ASC commitment in WAT, thereby increasing the risk of obesity later in life. Full article

Wound healing progresses through four phases: hemostasis, inflammation, proliferation, and remodeling. Wounds may become chronic if this process is disrupted. The use of small extracellular vesicle (sEV; EVs < 200 nm) exosomes (exo; ~40–120 nm) derived from human adipose stem cells (hASCs) as a treatment for wounds is well studied. The cargo of these exosomes is of great interest as this accelerates wound healing. Our previous studies identified lncRNAs GAS5 and MALAT1 as packaged and enriched in hASC exosomes. In this study, we use a rat model to examine the effects on wound healing when hASC exosomes are depleted of GAS5 and MALAT1. Rats were wounded and wounds were treated with 100 μg hASC_exo or hASC_exo-G-M every 2 days for 1 week. qPCR was completed to evaluate the molecular effects of depletion of GAS5 and MALAT1 from hASC_exo. RNAseq was performed on wound tissue to evaluate the molecular mechanisms changed by hASC_exo-G-M in wound healing. While hASC_exo-G-M significantly improved wound healing rate compared to control wounds, healing occurred slower than in wounds treated with hASC_exo that were not depleted of GAS5 and MALAT1. Overall, this study reveals that molecular functions associated with healing are reduced in the absence of GAS5 and MALAT1, highlighting the importance of these lncRNAs. Full article

Cell therapy utilizing mesenchymal stromal cells (MSCs) through paracrine mechanisms holds promise for regenerative purposes. Peritoneal fibrosis (PF) is a significant complication of peritoneal dialysis. Various strategies have been proposed to protect the peritoneal membrane (PM). This study explores the effectiveness of adipose-tissue-derived stem cells (ASCs) and extracellular vesicles (EVs) at mitigating PF using a rat model of PF induced by chlorhexidine gluconate. ASC and EV treatments effectively prevented an increase in the thickness of the PM and diminished the number of myofibroblasts, fibronectin expression, collagen III expression, and PF-related factors such as TGF-β and FSP-1. Smad3 gene expression decreased in the treatment groups, whereas Smad7 gene expression increased in treated animals. In addition, ASC and EV injections showed potent anti-inflammatory effects. Glucose transport through the PM remained unaffected in relation to the PF group; both treatments promoted an increase in ultrafiltration (UF) capacity. The PF+EVs treated group showed the highest increase in UF capacity. Another critical aspect of ASC and EV treatments was their impact on neoangiogenesis in the PM which is vital for UF capacity. Although the treated groups displayed a significant decrease in VEGF expression in the PM, peritoneal function remained effective. In conclusion, within the experimental PF model, both ASC and EV treatments demonstrated anti-inflammatory effects and comparably hindered the progression of PF. The EV treatment exhibited superior preservation of peritoneal function, along with enhanced UF capacity. These findings suggest the potential of ASCs and EVs as novel therapeutic approaches to prevent the development of PF associated with peritoneal dialysis. Full article

Nanocomposite hydrogels are gaining significant attention for biomedical applications in soft tissue engineering due to the increasing demand for highly flexible and durable soft polymer materials. This research paper focused on investigating and optimizing a procedure for the development of novel nanocomposite hydrogels based on poly(2-hydroxyethyl methacrylate)-co-(2-acrylamido-2-methylpropane sulfonic acid) (HEMA/AMPSA) copolymers. These hydrogels were synthesized through a grafting-through process, where the polymer network was formed using a modified clay crosslinker. The layered double hydroxide (LDH) clay modified with 3-(trimethoxysilyl)propyl methacrylate (ATPM) was synthesized using a novel recipe through a two-step procedure. The nanocomposite hydrogel compositions were optimized to achieve soft hydrogels with high flexibility. The developed materials were analyzed for their mechanical and morphological properties using tensile and compressive tests, transmission electron microscopy (TEM), scanning electron microscopy (SEM), and micro-computed tomography (micro-CT). The swelling behavior, network density, and kinetic diffusion mechanism demonstrated the specific characteristics of the materials. The modified LDH-ATPM was further characterized using Thermogravimetry (TGA), FTIR-ATR and X-ray diffraction (XRD). Biological assessments on human adipose-derived stem cells (hASCs) were essential to evaluate the biocompatibility of the nanocomposite hydrogels and their potential for soft tissue applications. Full article

Background: Adipose-derived mesenchymal stem cell conditioned medium (ASC-CM) improved the viability and wound closure of human tenocytes (HTCN) exposed to high glucose (HG) by activating the transforming growth factor beta 1 (TGF-β1) pathway. Objectives: Since ASC-CM can also modulate microRNAs (miRNAs) in recipient cells, this study investigated the effects of ASC-CM on the miRNAs regulating tendon repair (miR-29a-3p, miR-210-3p and miR-21-5p) in HG-HTNC. Methods: ASC-CM was obtained by ASCs isolated from the abdominal fat tissue of seven non-diabetic patients. HTNC were cultured in HG for 20 days, then scratched and exposed for 24 h to ASC-CM. qRT-PCR and ELISAs assessed miRNA and target levels. Results: HG-HTNC exhibited a significant downregulation of miRNAs. ASC-CM restored the levels of miRNAs and their related targets involved in tendon repair. Conclusions: The epigenetic modulation observed in HG-HTNC exposed to ASC-CM could be an innovative option in the management of diabetic tendinopathy. Full article

Background: Tendon rupture repair can result from fibrotic scar formation through imbalanced ECM deposition during remodeling. The tissue inhibitors of matrix metalloprotease (TIMPs) not only decrease ECM degradation, regulated by matrix metalloproteases (MMPs), but also restrict TGF-β1 activation and thus diminish fibrosis. Methods: Rabbit tenocytes (rbTenocytes) and rabbit adipose-derived stem cells (rbASCs) were cultivated under different TIMP-1 concentrations. Proliferation and gene expression were assessed. TIMP-1 was incorporated into emulsion electrospun DegraPol^® (DP) tubes that were characterized by SEM for fiber thickness, pore size, and wall thickness. Static and dynamic water contact angles, FTIR spectra, and TIMP-1 release kinetics were determined. Results: While the proliferation of rbTenocytes and rbACS was not affected by TIMP-1 supplementation in vitro, the gene expression of Col1A1 was increased in rbTenocytes, the gene expression of ki67 was increased in both cell types, the gene expression of tenomodulin was increased in both cell types at 100 ng/mL TIMP-1, and alkaline phosphatase expression ALP rose significantly in rbASCs. Electrospun TIMP-1/DP fibers had a ~5 μm diameter, a ~10 μm pore size, and a mesh thickness of ~200 μm. TIMP-1/DP meshes were more hydrophilic than pure DP meshes. TIMP-1 was released from the meshes with a sustained release of up to 7 days. Conclusions: TIMP-1/DP tubes may be used to modulate the fibrotic tissue reaction when applied around conventionally sutured tendon ruptures. Full article