Mesenchymal stem cell-derived extracellular vesicles ameliorate heat stroke-induced hippocampal injury and modulate VIM-AS1-associated miR-34a-5p/Per2 signaling
Overview
- Department of Critical Care Medicine, the Fifth Medical Centre, Chinese PLA General Hospital, Beijing, China
- National Key Laboratory of Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, National Clinical Research Center for Kidney Diseases, Beijing, China
- Medical School of Chinese PLA, Beijing, China
- Department of Critical Care Medicine, the First Medical Centre, Chinese PLA General Hospital, Beijing, China
- Department of Critical Care Medicine, Beijing Armed Police Corps Hospital, Beijing, China
- Department of Emergency Medicine, the First Medical Centre, Chinese PLA General Hospital, Beijing, China
- Department of Critical Care Medicine, PLA General Hospital of Southern Theatre Command, Guangzhou, China
- Department of Basic Medicine, Medical School of Chinese PLA, Beijing, China
Abstract
Background: Central nervous system (CNS) injury is a major determinant of mortality and persistent disability after heat stroke. Mesenchymal stromal/
Methods: Human umbilical cord MSC-EVs were isolated by differential ultracentrifugation and characterized by transmission electron microscopy, nanoparticle tracking analysis, and immunoblotting for EV-enriched and non-EV markers. In a mouse heat stroke model, MSC-EVs (200 μg total protein per mouse) were administered intravenously. Neurological outcomes, hippocampal pathology, inflammatory mediators, IBA1 immunoreactivity, and phenotype-associated markers were evaluated. BV2 heat-stress and MSC co-culture experiments were used to examine VIM-AS1-associated miR-34a-5p/
Results: MSC-EV treatment improved survival and neurological scores and reduced hippocampal injury and inflammatory readouts after heat stroke. In mouse brain and BV2 models, treatment was associated with lower expression of inflammatory-associated markers and higher expression of repair-associated markers. EV RNA sequencing identified abundant VIM-AS1. VIM-AS1 gain- and loss-of-function experiments altered miR-34a-5p and Per2 expression, while miR-34a-5p directly repressed a conserved mouse Per2 3′UTR reporter. VIM-AS1 overexpression also improved inflammatory and neurological readouts in vivo.
Conclusions: MSC-EVs attenuated heat stroke-induced hippocampal injury and were associated with coordinated changes in VIM-AS1, miR-34a-5p, and Per2. These findings support MSC-EVs and VIM-AS1-associated signaling as candidates for further mechanistic investigation, while not establishing VIM-AS1 as the sole or dominant active EV cargo.
Reproduced under the paper's license (CC BY), from the paper cited above.
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Data
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- figshare:33421912 — at figshare; found in “Data availability statement”
Data availability statement
The data presented in the study are deposited in the Figshare repository, accession number https://
Reproduced under the paper's license (CC BY), from the paper cited above.
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Version 1, 29 September 2026: the first record
Recorded: type, language, journal, volume, pages, dates, 11 authors, 5 keywords, 48 references, 1 RRID.
Cite
This paper
Wang, L., Wang, M., Liu, Y., Bai, Y., Li, Y., Cao, Y., Wang, C., Gao, Z., Wu, Y., Deng, Z., & Kang, H. (2026). Mesenchymal stem cell-derived extracellular vesicles ameliorate heat stroke-induced hippocampal injury and modulate VIM-AS1-associated miR-34a-5p/
BibTeX
@article{wang2026mesench
author = {Wang, Lu and Wang, Min and Liu, Yuyan and Bai, Yang and Li, Yun and Cao, Yuan and Wang, Chengjin and Gao, Zhen and Wu, Yiqi and Deng, Zihui and Kang, Hongjun},
title = {{Mesenchymal stem cell-derived extracellular vesicles ameliorate heat stroke-induced hippocampal injury and modulate VIM-AS1-associated miR-34a-5p/
journal = {Frontiers in immunology},
year = {2026},
month = sep,
volume = {17},
pages = {1873819},
publisher = {Frontiers Media SA},
issn = {1664-3224},
pmcid = {PMC13616672}
}
RIS
TY - JOUR
AU - Wang, Lu
AU - Wang, Min
AU - Liu, Yuyan
AU - Bai, Yang
AU - Li, Yun
AU - Cao, Yuan
AU - Wang, Chengjin
AU - Gao, Zhen
AU - Wu, Yiqi
AU - Deng, Zihui
AU - Kang, Hongjun
TI - Mesenchymal stem cell-derived extracellular vesicles ameliorate heat stroke-induced hippocampal injury and modulate VIM-AS1-associated miR-34a-5p/
T2 - Frontiers in immunology
J2 - Front Immunol
PY - 2026
DA - 2026/
VL - 17
SP - 1873819
SN - 1664-3224
PB - Frontiers Media SA
LA - en
ER -
CSL-JSON
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