Work

Mesenchymal stem cell-derived extracellular vesicles in diabetes: immunomodulation and therapeutic prospects

Year: 2026

Type: review

Abstract: Diabetes mellitus is characterized by chronic hyperglycemia, immune dysregulation, and progressive multi-organ injury. Mesenchymal stem cell-derived extracellular vesicles(MSC-EVs) have emerged as cell-free mediators capable of transferring bioactive cargo and modulating immune, metabolic, and regenerative responses. This narrative review summarizes current evidence on the roles of MSC-EVs in diabetes, focusing on immune-cell regulation, pancreatic β-cell protection, metabolic homeostasis, and major complications, while also considering EV isolation, engineering, delivery, and clinical translation. Preclinical studies indicate that MSC-EVs can modulate T-cell, macrophage, dendritic-cell, B-cell, natural killer-cell, innate lymphoid-cell, and complement-associated responses; reduce inflammatory and oxidative injury; protect β cells from apoptosis; improve insulin signaling; and promote tissue repair in diabetic wounds, kidney disease, retinopathy, neuropathy, cardiovascular injury, bone metabolic disorders, and erectile dysfunction. These effects are mediated by preparation-specific cargo and signaling pathways, including miRNAs, proteins, programmed death-ligand 1(PD-L1)/PD-1 signaling, Phosphoinositide 3-kinase/Protein Kinase B(PI3K/Akt)-related pathways, and phosphatase and tensin homolog(PTEN)/AKT signaling. The review also distinguishes direct diabetes-specific evidence from mechanistic background derived from non-diabetic models. However, the evidence remains heterogeneous across MSC sources, EV preparations, experimental models, doses, and delivery strategies, and current clinical evidence is still limited. Registered investigations should therefore be distinguished from studies reporting clinical outcomes, and product-specific efficacy should not be inferred from trial registration alone. Overall, MSC-EVs represent a promising but not yet established therapeutic platform for diabetes. Future translation will require standardized terminology and characterization, scalable manufacturing, reproducible potency assessment, optimized targeting and dosing, long-term safety evaluation, and well-designed product-specific clinical trials.

Source: Frontiers in Immunology

DOI: 10.3389/fimmu.2026.1918124