isolation-therapeutic-application-extracellular-vesicles-derived-from

Isolation and Therapeutic Application of Extracellular Vesicles Derived from Self-Assembled Mesenchymal Stem Cell Aggregates

Extracellular vesicles (EVs) are vital mediators of intercellular communication and promising cell-free agents for regenerative medicine. Among EV ...

The Fourth Military Medical University

Lipid metabolic disorder (LMD) serves as a systemic driver of osteoporosis (OP), with jawbone osteoporosis (JOP) representing a clinically significant yet underexplored complication. Current clinical treatments for JOP remain suboptimal, highlighting the need for innovative approaches. The use of metabolic regulators represents a promising therapeutic strategy for OP management. While brown adipose tissue-derived extracellular vesicles (BEV) exhibit metabolic regulatory potential, their capacity to mitigate LMD-associated OP remains unclear.

Brown adipose tissue-derived extracellular vesicles regulate hepatocyte mitochondrial activity to alleviate high-fat diet-induced jawbone osteoporosis in mice.

Type 2 diabetes (T2D) is a prevalent metabolic disease inducing alterations of multiple organ systems with currently no cure. Extracellular vesicles (EVs) have been increasingly noticed as one critical paracrine communicator inducing insulin resistance and metabolic disorders in T2D, but clinically available pharmaceuticals for controlling pathological EV release is lacking. Here, we discover that the natural monosaccharide D-mannose exists with an altered level in the db/db mouse T2D model. Intriguingly, oral administration of D-mannose with the drinking water safely ameliorates diabetic symptoms in db/db mice. D-mannose administration does not critically regulate the gut microbiome and circulatory T lymphocytes in treating T2D, while administrated D-mannose rapidly accumulates in the liver, alleviates hepatic steatosis and rescues insulin resistance. Regarding the mechanism, the T2D pathological EVs released by macrophages are targeted and reduced by D-mannose, which metabolically inhibits CD36 expression and restores function of hepatocytes. Importantly, by regulating macrophage EV release, D-mannose administration reveals extra-hepatic benefits and retards diabetic bone loss. Taken together, our findings unveil D-mannose as a candidate T2D therapeutic and highlight sugars governing intercellular EV crosstalk, paving an avenue for pharmaceutical T2D approaches with amelioration of multi-organ deteriorations.

D-Mannose Alleviates Type 2 Diabetes and Rescues Multi-Organ Deteriorations by Controlling Release of Pathological Extracellular Vesicles.

 To investigate the therapeutic potential and underlying mechanism of mesenchymal stem cell (MSC)-derived extracellular vesicles (MSC-EVs) in treating hepatorenal syndrome (HRS), a condition lacking therapies for multi-organ damage.  EVs were isolated from human umbilical cord MSCs and characterized by transmission electron microscopy, nanoparticle tracking analysis, and proteomics. A murine model of HRS, induced by bile duct ligation (BDL), was established, and mice received intravenous MSC-EVs treatment. Therapeutic efficacy was assessed through histopathology, serum biochemistry, and analysis of necroptosis, inflammation, and fibrosis markers.  Proteomic profiling of MSC-EVs revealed significant enrichment of proteins involved in renal processes, anti-fibrosis, and immune regulation. In BDL-induced HRS mice, MSC-EVs treatment demonstrated potent multi-organ protective effects. This was evidenced by alleviation of hepatic necroptosis and renal tubular injury, downregulation of interleukin-17 expression, and concurrent attenuation of fibrosis in both liver and kidney tissues. Consequently, significant improvements in hepatic and renal function markers were observed.  MSC-EVs represent a novel and effective cell-free nanotherapeutic strategy for HRS. They confer protection through multi-faceted mechanisms, including inhibition of necroptosis, immune reprogramming, and fibrosis resolution, offering a promising paradigm for the treatment of multi-organ failure.

Multiorgan repair by MSC-derived extracellular vesicles in hepatorenal syndrome through necroptosis alleviation, immune reprogramming and fibrosis resolution.

Article	Year
Brown adipose tissue-derived extracellular vesicles regulate hepatocyte mitochondrial activity to alleviate high-fat diet-induced jawbone osteoporosis in mice. Frontiers in endocrinology\| PubMed ID: 40343072	2025
D-Mannose Alleviates Type 2 Diabetes and Rescues Multi-Organ Deteriorations by Controlling Release of Pathological Extracellular Vesicles. Exploration (Beijing, China)\| PubMed ID: 41163804	2025
Multiorgan repair by MSC-derived extracellular vesicles in hepatorenal syndrome through necroptosis alleviation, immune reprogramming and fibrosis resolution. Extracellular vesicles and circulating nucleic acids\| PubMed ID: 41988479	2026

Zhen Gong

Biography

JoVE Journal Publications

Other Publications