Mesenchymal stem cell-derived extracellular vesicles in diabetes: immunomodulation and therapeutic prospects
- 1Department of endocrinology and metabolism, China-Japan Union Hospital of Jilin University
- 2Department of Cardiac Superficial Musculoskeletal Ultrasound, Songyuan Central Hospital
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.
Related
- Mesenchymal Stem/Stromal Cell-Derived Extracellular Vesicles for Immunomodulation in Osteoarthritis
- Extracellular Vesicles in Molecular Crosstalk and Disease Pathogenesis: A Comprehensive Review on Mechanisms and Therapeutic Prospects
- Pulsed Focused Ultrasound–Mediated Mechanopriming Enhances the Therapeutic Efficacy of Mesenchymal Stromal Cell–Derived Extracellular Vesicles in Acute Respiratory Distress Syndrome
- Adipose-derived stem cell-derived extracellular vesicles promote critical-sized bone defect repair by enhancing the homing of bone marrow mesenchymal stem cells
- Epithelial-endothelial barrier dysfunction and oxidative stress in ARDS subphenotypes: comparative efficacy of extracellular vesicles derived from bone marrow (MSC-EVs) and adipose tissue (ASC-EVs) mesenchymal stem cells
BibTeX
@article{ma2026mesenchymal,
title = {{Mesenchymal stem cell-derived extracellular vesicles in diabetes: immunomodulation and therapeutic prospects}},
author = {Lingli Ma and Ning Hou and Xuejiao Zhang and Xiaoyu Zhao and Qing Liu and Yan Zhang and Jiajing Dong and Zimeng Li and Qing Wang},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1918124},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1918124/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Mesenchymal stem cell-derived extracellular vesicles in diabetes: immunomodulation and therapeutic prospects
AU - Lingli Ma
AU - Ning Hou
AU - Xuejiao Zhang
AU - Xiaoyu Zhao
AU - Qing Liu
AU - Yan Zhang
AU - Jiajing Dong
AU - Zimeng Li
AU - Qing Wang
PY - 2026
DA - 2026/10/19
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1918124
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1918124/full
AB - 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.
SN - 1664-3224
ER -