Adipose-derived stem cell extracellular vesicles in diabetic microangiopathy: from pathological networks to clinical translation
- 1Key Laboratory of Medical Electrophysiology, Ministry of Education & Medical Electrophysiological Key Laboratory of Sichuan Province (Collaborative Innovation Center for Prevention of Cardiovascular Diseases), Institute of Cardiovascular Research, Southwest Medical University
- 2School of Basic Medical Sciences, Southwest Medical University
- 3Laboratory for Drug Discovery and Druggability Evaluation of Sichuan Province, Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica, Southwest Medical University
Abstract
Diabetic microangiopathy (DMA) is a major cause of morbidity and mortality in diabetes. Its pathogenesis involves interconnected processes, including metabolic disturbance, oxidative stress, inflammation, immune dysregulation, endothelial dysfunction, mitochondrial abnormalities, and impaired tissue repair. This complexity suggests that therapeutic strategies targeting individual pathways may be insufficient to address the multidimensional pathological processes underlying DMA. Adipose-derived stem cell-derived extracellular vesicles (ADSC-EVs) have emerged as potential cell-free therapeutic candidates whose multimolecular cargo may modulate multiple disease-relevant processes. Preclinical evidence suggests that ADSC-EVs can influence oxidative stress, inflammation, angiogenesis, immune responses, and tissue repair, providing a potential basis for multitarget modulation of pathological microenvironments. This review critically evaluates organ-specific evidence for ADSC-EVs in diabetic retinopathy, diabetic kidney disease, diabetic peripheral neuropathy, and diabetic chronic wounds, with particular attention to evidence specificity, therapeutic mechanisms, delivery barriers, and translational limitations. We further summarize advances in EV engineering, including parent-cell and cargo engineering, surface modification, biomaterial integration, and stimuli-responsive delivery, while distinguishing ADSC-EV-specific findings from evidence extrapolated from the broader EV field. Finally, we discuss major barriers to clinical translation, including manufacturing standardization, potency assessment, biodistribution, organ-specific delivery, long-term safety, and regulatory evaluation. Future studies integrating disease stratification, multi-omics, rational engineering, and standardized manufacturing may help determine whether the multitarget effects of ADSC-EVs can be translated into reproducible and clinically meaningful therapies for DMA.
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BibTeX
@article{zhu2026adiposederived,
title = {{Adipose-derived stem cell extracellular vesicles in diabetic microangiopathy: from pathological networks to clinical translation}},
author = {Xinggui Zhu and Wenyan Yang and Yujie Ni and Yongyi Li and Jianming Wu and Yi Han and Qiaozhi Wang},
journal = {Frontiers in Pharmacology},
year = {2026},
month = oct,
doi = {10.3389/fphar.2026.1970641},
url = {https://www.frontiersin.org/articles/10.3389/fphar.2026.1970641/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Adipose-derived stem cell extracellular vesicles in diabetic microangiopathy: from pathological networks to clinical translation
AU - Xinggui Zhu
AU - Wenyan Yang
AU - Yujie Ni
AU - Yongyi Li
AU - Jianming Wu
AU - Yi Han
AU - Qiaozhi Wang
PY - 2026
DA - 2026/10/26
JO - Frontiers in Pharmacology
DO - 10.3389/fphar.2026.1970641
UR - https://www.frontiersin.org/articles/10.3389/fphar.2026.1970641/full
AB - Diabetic microangiopathy (DMA) is a major cause of morbidity and mortality in diabetes. Its pathogenesis involves interconnected processes, including metabolic disturbance, oxidative stress, inflammation, immune dysregulation, endothelial dysfunction, mitochondrial abnormalities, and impaired tissue repair. This complexity suggests that therapeutic strategies targeting individual pathways may be insufficient to address the multidimensional pathological processes underlying DMA. Adipose-derived stem cell-derived extracellular vesicles (ADSC-EVs) have emerged as potential cell-free therapeutic candidates whose multimolecular cargo may modulate multiple disease-relevant processes. Preclinical evidence suggests that ADSC-EVs can influence oxidative stress, inflammation, angiogenesis, immune responses, and tissue repair, providing a potential basis for multitarget modulation of pathological microenvironments. This review critically evaluates organ-specific evidence for ADSC-EVs in diabetic retinopathy, diabetic kidney disease, diabetic peripheral neuropathy, and diabetic chronic wounds, with particular attention to evidence specificity, therapeutic mechanisms, delivery barriers, and translational limitations. We further summarize advances in EV engineering, including parent-cell and cargo engineering, surface modification, biomaterial integration, and stimuli-responsive delivery, while distinguishing ADSC-EV-specific findings from evidence extrapolated from the broader EV field. Finally, we discuss major barriers to clinical translation, including manufacturing standardization, potency assessment, biodistribution, organ-specific delivery, long-term safety, and regulatory evaluation. Future studies integrating disease stratification, multi-omics, rational engineering, and standardized manufacturing may help determine whether the multitarget effects of ADSC-EVs can be translated into reproducible and clinically meaningful therapies for DMA.
SN - 1663-9812
ER -