Search Results (151)

The global obese population accounts for approximately 30% of the total population and continues to increase. White adipocytes, which accumulate in the body for energy storage, are associated with obesity. Mechanisms that activate browning of white adipocytes are an attractive therapeutic target for obesity and metabolic disorders. Exosomes are nano-sized biovesicles that play a role in cell-to-cell communication though the transfer of cargos such as microRNAs. Although milk exosomes contain many endogenous microRNA molecules, the role of microRNAs in milk exosomes is limited. Therefore, the aim of this study was to investigate the effects of milk exosomes on the browning of white adipocyte. Mouse pre-adipocytes (3T3-L1) and human adipose-derived stem cells (hADSCs) were differentiated and exposed to milk exosomes. Compared to control, milk exosomes promoted the expression of thermogenic genes and cellular mitochondrial energy metabolism in both 3T3-L1 cells and hADSCs. Additionally, milk exosomes were orally administered to mice fed a high-fat diet. As the intake of milk exosomes increased, the mice’s body weight decreased. Milk exosomes also increased the protein levels of thermogenic genes and mitochondrial-related genes in mouse adipose tissue. The overexpression of miR-11987, which is abundant in milk exosomes, in both 3T3-L1 cells and hADSCs led to the increased expression of thermogenic genes and mitochondrial activity. Our results support that bovine-specific miR-11987 in milk exosomes promotes the browning of white adipocytes. Therefore, milk exosome and milk exosomal miR-11987 could have significant clinical implications for obesity and metabolic syndrome. Full article

Osteoarthritis (OA) is a prevalent and debilitating joint disorder that affects a substantial proportion of the global population, underscoring the urgent need for therapeutic strategies that extend beyond symptomatic management. Although mesenchymal stem cells (MSCs) have emerged as a promising therapeutic modality, their clinical application remains constrained by several inherent limitations. This study explores a cell-free alternative by investigating the therapeutic potential of exosomes derived from bone marrow (BMSCs), adipose tissue (ADSCs), and umbilical cord (UMSCs) MSCs in mitigating OA pathogenesis, utilizing both in vitro and ex vivo models. Exosomes from each MSC source were isolated and characterized through nanoparticle tracking analysis, transmission electron microscopy, and Western blotting to confirm their identity and purity. Subsequently, their chondroprotective, anti-inflammatory, and regenerative properties were systematically assessed through evaluations of cell viability, expression profiles of inflammatory and chondroprotective markers, and chondrocyte migration assays. The results demonstrate that all three types of MSC-derived exosomes (MSC-Exos) exhibit low cytotoxicity while significantly suppressing proinflammatory markers and enhancing the expression of chondroprotective genes. Notably, BMSC-Exos and UMSC-Exos displayed superior efficacy in attenuating inflammation, promoting cartilage protection, and inhibiting chondrocyte apoptosis. Furthermore, all MSC-Exos markedly enhanced chondrocyte motility, a critical component of cartilage repair. Collectively, these findings support the therapeutic promise of MSC-Exos, particularly those derived from BMSCs and UMSCs, as a targeted, cell-free approach for the treatment of OA compared to ADSCs. By modulating inflammation, promoting cartilage regeneration, and preventing chondrocyte apoptosis, MSC-Exos may serve as a viable and scalable alternative to current MSC-based therapies for this widespread degenerative disease. Full article

Coronary artery disease (CAD) remains a leading cause of global morbidity and mortality despite advances in medical and interventional therapies. Mesenchymal stem cell (MSC) therapy has emerged as a promising regenerative approach for patients with refractory or non-revascularizable CAD. MSCs exhibit unique immunomodulatory, pro-angiogenic, and anti-fibrotic properties, primarily through paracrine mechanisms involving the secretion of cytokines, growth factors, and exosomal microRNAs. Clinical and preclinical studies have demonstrated improvements in myocardial perfusion, left ventricular ejection fraction (LVEF), and functional capacity following MSC-based interventions, particularly in patients with low baseline LVEF and heightened inflammation. Various MSC sources—including bone marrow, adipose tissue, and umbilical cord—offer distinct advantages, while delivery strategies such as intracoronary, intramyocardial, intravenous, and subcutaneous administration impact cell retention and efficacy. Advances in genetic modification, hypoxic preconditioning, and exosome-based therapies aim to enhance MSC survival and therapeutic potency. However, challenges persist regarding cell engraftment, cryopreservation effects, and inter-patient variability. Moving toward precision cell therapy, future approaches may involve stratifying patients by inflammatory status, ischemic burden, and comorbidities to optimize treatment outcomes. MSCs may not yet replace conventional therapies but are increasingly positioned to complement them within a personalized, regenerative framework for CAD management. 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

Background: Whether intestinal epithelial cells can regulate distant adipose tissue remains a mystery. Methods: Cold-stimulated intestinal epithelial cell-derived exosomes (Cold IEC-Exo) play a pivotal role in enhancing adipose thermogenesis and metabolic homeostasis, as demonstrated in this study. Results: IEC-Exo can accumulate in adipose tissue. Compared with IEC-Exo derived from room temperature mice (RT IEC-Exo), Cold IEC-Exo significantly enhanced the thermogenesis of adipose. In vitro, Cold IEC-Exo directly stimulated thermogenesis in primary adipocytes by elevating oxygen consumption rate, proton leak, and fatty acid uptake, with no effect on glucose uptake. Small RNA sequencing identified miR-674-3p as a key mediator enriched in Cold IEC-Exo. miR-674-3p mimicry replicated Cold IEC-Exo effects, augmenting Ucp1 expression, mitochondrial uncoupling, and fatty acid utilization in adipocytes. Local overexpression of miR-674-3p in BAT and sWAT via AAV in vivo enhanced thermogenesis and attenuated diet-induced glucose intolerance. Conclusions: These findings establish that Cold IEC-Exo, via miR-674-3p transfer, drive adipose thermogenic activation and mitigate metabolic dysfunction, highlighting their therapeutic potential in obesity-related disorders. 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

Exosomes are actively produced extracellular vesicles, released from different cell types, that exert important regulatory roles in vital cellular functions. Tumor-derived exosomes (TDEs) have received increasing attention because they enable intercellular communication between the neoplastic and non-neoplastic cells present in the microenvironment of tumors, affecting important functions of different types of mesenchymal stem cells (MSCs) with the ability to self-renew and differentiate. MSC-derived exosomes (MSC-exos) carry a variety of bioactive molecules that can interact with specific cellular targets and signaling pathways, influencing critical processes in tumor biology, and exhibiting properties that either promote or inhibit tumor progression. They can regulate the tumor microenvironment by modulating immune responses, enhancing or suppressing angiogenesis, and facilitating tumor cells’ communication with distant sites, thus altering the behavior of non-cancerous cells present in the microenvironment. Herein, we explore the main functions of TDEs and their intricate interactions with MSC-exos, in terms of enhancing cancer progression, as well as their promising clinical applications as tumor microenvironment modulators. Full article

Background: Fine dust exposure worsens oily skin by disrupting lipid metabolism and triggering oxidative inflammation. Scutellaria baicalensis extract-induced exosomes (SBEIEs) have shown anti-inflammatory effects by suppressing reactive oxygen species (ROS) and lipid-regulating properties, making them potential therapeutic agents. Methods: Exosomes from fibroblasts treated with SBEIEs and PM10 were tested on macrophages, adipose-derived stem cells (ASCs), and T lymphocytes. ELISA, flow cytometry, and PCR measured cytokines and gene expression. A 10-day clinical trial evaluated skin hydration, oiliness, and inflammation. Results: SBEIEs increased IRF3 (1.6 times) and suppressed PPARγ in ASCs while enhancing lipolysis markers. Sebaceous gland activity (squalene synthase) decreased by 10%. Macrophages showed increased IRF3, IFN-β, and IL-10 (2.1 times). T cells secreted IL-4 and IL-22 (2–2.33 times). Clinically, SBEIEs improved hydration (21%), reduced oiliness (1.6 times), and decreased inflammation (2.2 times). Conclusions: SBEIEs effectively regulate lipid metabolism, cytokines, and immune responses, showing promise to treat oily and inflamed skin caused by fine dust exposure. Further studies are needed for clinical applications. Full article

Systemic sclerosis (SSc) is a complex autoimmune disease characterized by vasculopathy and tissue fibrosis affecting the skin and internal organs. Genetic and environmental factors influence susceptibility, severity, and onset. Current treatments are limited and not always effective, leading researchers to investigate new approaches, such as the use of adipose-derived mesenchymal stem cells (ADSCs) through fat grafting. This review seeks to understand how ADSCs may impact the development and progression of SSc, with a particular focus on how these cells could alter immune responses and reduce fibrosis. ADSCs have been found to affect various immune cells, including T cells, B cells, macrophages, and dendritic cells, by releasing cytokines, chemokines, and growth factors. These interactions generally suppress inflammation and promote a regulatory immune environment. Additionally, ADSCs can influence the extracellular matrix, helping to prevent fibrosis through signaling molecules like exosomes. ADSCs show promise as a treatment for SSc due to their ability to modulate the immune system and reduce fibrosis. Early clinical studies are encouraging, but more research is needed to fully understand how they work and to develop effective treatment protocols. Full article

Adipose tissue is responsible for fat storage and is an important producer of extracellular vesicles (EVs). The biological content of exosomes, one kind of EV, provides information on aspects such as immunometabolic alterations. This study aimed to compare three plasma exosome isolation methods—using a commercial kit (CK), size exclusion chromatography (SEC), and differential centrifugation (DC)—and select the best one. Individuals categorized by normal and high body fat percentages were used. The DC and CK were proven to be the most advantageous out of the exosome isolation methods, so we suggest these methods for further protein and molecular analyses, respectively. Still, we emphasize the importance of selecting an appropriate methodology depending on the specific research objectives. At the same time, no statistical differences in exosome quality, morphology, total protein, or microRNA concentration were observed between individuals categorized by body fat percentage, so we suggest that the exosomal cargo varies in individuals with normal and high fat percentages. Full article

Exosomes can transport regulatory biomolecules and are mediators of cellular signaling among metabolic tissues through endocrine mechanisms. Understanding the pathways and processes underlying exosome-mediated inter-tissue communication is critical for elucidating the molecular pathophysiology of metabolic diseases such as obesity, type 2 diabetes mellitus (T2DM), and cardiovascular disorders. Consequently, these mechanisms represent novel and promising targets for pharmacological regulation. We examined the current knowledge regarding exosome physiology, the mechanisms of interaction with target tissues, and its role in metabolic tissue communication. We also analyzed the secretory profiles of exosomes in metabolic tissues, emphasizing their regulatory roles in adipose tissue, liver, pancreas, skeletal muscle, and the small intestine, while discussing their association with metabolic diseases. In this sense, we propose the exosomal pentad as a novel framework highlighting exosome-mediated inter-organ communication, where exosomes may regulate a metabolic axis involving these tissues. This model aligns with the ominous octet in type 2 diabetes but emphasizes exosomes as key regulators of metabolic homeostasis and potential therapeutic targets. The role of exosomes for the treatment of metabolic diseases emerges as a critical area of pharmacologic exploration. For instance, therapeutic strategies that prevent target tissue binding or expression of cargo molecules such as miRNAs could be designed, using antagomiRs or nanoparticles. Additionally, integrins like αvβ5 on the exosomal membrane can be blocked with monoclonal antibodies or engineered for targeted delivery of therapeutic molecules. Exosomes, critical mediators of inter-organ communication and metabolic regulation, hold potential to design precise molecular-level therapies while minimizing systemic side effects. Full article

Ovarian cancer (OC) is characterized by high mortality rates due to late diagnosis, recurrence, and metastasis. Here, we show that extracellular signaling molecules secreted by adipose-derived mesenchymal stem cells (ASCs) and OC cells—either in the conditioned medium (CM) or within small extracellular vesicles (sEVs)—modulate cellular responses and drive OC progression. ASC-derived sEVs and CM secretome promoted OC cell colony formation, invasion, and migration while upregulating tumor-associated signaling pathways, including TGFβ/Smad, p38MAPK/ERK1/2, Wnt/β-catenin, and MMP-9. Additionally, OC-derived sEVs and CM induced a pro-tumorigenic phenotype in ASCs, enhancing their invasiveness and expression of tumor-associated factors. Notably, both ASCs and OC cells exhibited increased expression of E-cadherin and Snail/Slug proteins, key markers of epithelial/mesenchymal hybrid phenotype, enhancing cellular plasticity and metastatic potential. We also demonstrated that these cellular features are, at least in part, due to the presence of tumor-supportive molecules such as TNF-α, Tenascin-C, MMP-2, and SDF-1α in the CM secretome of ASCs and OC cells. In silico analyses linked these molecular changes to poor prognostic outcomes in OC patients. These findings highlight the critical role of sEVs and tumor/stem cell-derived secretome in OC progression through bidirectional interactions that impact cellular behavior and phenotypic transitions. We suggest that targeting EV-mediated communication could improve therapeutic strategies and patient outcomes. Full article

The use of autologous biological preparations (ABPs) and their combinations fills the void in healthcare treatment options that exists between surgical procedures, like plastic reconstructive, cosmetic, and orthopedic surgeries; non-surgical musculoskeletal biological procedures; and current pharmaceutical treatments. ABPs, including high-density platelet-rich plasma (HD-PRP), bone marrow aspirate concentrates (BMACs), and adipose tissue preparations, with their unique stromal vascular fractions (SVFs), can play important roles in tissue regeneration and repair processes. They can be easily and safely prepared at the point of care. Healthcare professionals can employ ABPs to mimic the classical wound healing cascade, initiate the angiogenesis cascade, and induce tissue regenerative pathways, aiming to restore the integrity and function of damaged tissues. In this review, we will address combining autologous HD-PRP with adipose tissue, in particular the tissue stromal vascular fraction (t-SVF), as we believe that this biocellular combination demonstrates a synergistic effect, where the HD-PRP constituents enhance the regenerative potential of t-SVF and its adipose-derived mesenchymal stem cells (AD-MSCs) and pericytes, leading to improved functional tissue repair, tissue regeneration, and wound healing in variety of clinical applications. We will address some relevant platelet bio-physiological aspects, since these properties contribute to the synergistic effects of combining HD-PRP with t-SVF, promoting overall better outcomes in chronic inflammatory conditions, soft tissue repair, and tissue rejuvenation. Full article

It is unknown whether there are differentially expressed proteins (DEPs) in the circulating exosomes of appropriate- vs. small-for-gestational-age (AGA vs. SGA) infants, and if so, whether such DEPs relate to measures of endocrine–metabolic health and body composition in childhood. Proteomic analysis in cord-blood-derived exosomes was performed by label-free quantitative mass spectrometry in AGA (n = 20) and SGA infants (n = 20) and 91 DEPs were identified. Enrichment analysis revealed that they were related to complement and coagulation cascades, lipid metabolism, neural development, PI3K/Akt and RAS/RAF/MAPK signaling pathways, phagocytosis and focal adhesion. Protein–protein interaction (PPI) analysis identified 39 DEPs involved in the pathways enriched by the KEGG and Reactome. Those DEPs were associated with measures of adiposity and insulin resistance and with liver fat at age 7 (all p < 0.01). Multivariate linear regression analysis uncovered that two DEPs (up-regulated in SGA), namely PCYOX1 (related to adipogenesis) and HSP90AA1 (related to lipid metabolism and metabolic-dysfunction-associated steatotic liver disease progression), were independent predictors of the hepatic fat fraction at age 7 (β = 0.634; p = 0.002; R² = 52% and β = 0.436; p = 0.009; R² = 24%, respectively). These data suggest that DEPs at birth may predict insulin resistance, adrenarche and/or ectopic adiposity in SGA children at age 7, when an early insulin-sensitizing intervention could be considered. Full article

Background: Traumatic brain injury (TBI) occurs in individuals of all ages, predominantly during sports, accidents, and in active military service members. Chronic consequences of TBI include declined cognitive and motor function, dementia, and emotional distress. Small extracellular vesicles (sEVs), previously referred to as exosomes, are nano-sized lipid vesicles that play a role in intercellular communication. Our prior research established the efficacy of sEVs derived from human adipose stem cells (hASC sEVs) in accelerating the healing of brain injuries. The hASC sEVs are a biologic therapeutic and need to be stored at −20 °C or −80 °C. This limits their use in translating to everyday use in clinics or their inclusion in first-aid kits for application immediately after injury. To address this, here we demonstrate that hASC sEVs can be stored at room temperature (RT) for two months post lyophilization. Methods: A transmission electron microscope (TEM) and nanoparticle tracking analysis (NTA) were used to validate the morphology of lyophilized RT sEVs. Using in vitro models of neuronal injury mimicking physical injury, inflammation, and oxidative stress, we demonstrate that lyophilized RT hASC sEVs are viable and promote the healing of neuronal injuries. Results: The lyophilized sEVs maintain their purity, size, and morphology upon rehydration. Lyophilized, RT stored sEVs showed better efficacy after two months compared with −80 °C stored sEVs. Conclusions: RT storage of lyophilized hASC sEVs maintains their efficacy to accelerate the healing of injuries in neuronal cells. This will advance the use of hASC sEVs, bringing them closer to use in clinics, home first-aid kits, and on battlefields by active service members. Full article