2026-10-14T15:14:16Z https://api.figshare.com/v2/oai

oai:figshare.com:article/33718291 2026-09-14T04:37:01Z category_696 portal_316 item_type_3 month_year_09_2026

Supplementary file 1_Mesenchymal stem cell-derived extracellular vesicles ameliorate heat stroke-induced hippocampal injury and modulate VIM-AS1-associated miR-34a-5p/Per2 signaling.docx Lu Wang (45927) Min Wang (21070) Yuyan Liu (385428) Yang Bai (198601) Yun Li (692280) Yuan Cao (150846) Chengjin Wang (1796197) Zhen Gao (609801) Yiqi Wu (6741323) Zihui Deng (8592381) Hongjun Kang (3467561) Genetic Immunology central nervous system exosomes heat stroke mesenchymal stem cells microglial cell Background<p>Central nervous system (CNS) injury is a major determinant of mortality and persistent disability after heat stroke. Mesenchymal stromal/stem cell-derived extracellular vesicles (MSC-EVs) are candidate cell-free immunomodulatory therapeutics, but their effects and molecular correlates in heat stroke-associated brain injury remain incompletely defined. We investigated whether MSC-EVs attenuate hippocampal inflammation and alter microglial phenotype-associated markers after heat stroke.</p>Methods<p>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/Per2 signaling.</p>Results<p>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.</p>Conclusions<p>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.</p> 2026-09-14T04:37:01Z Dataset Dataset 10.3389/fimmu.2026.1873819.s001 https://figshare.com/articles/dataset/Supplementary_file_1_Mesenchymal_stem_cell-derived_extracellular_vesicles_ameliorate_heat_stroke-induced_hippocampal_injury_and_modulate_VIM-AS1-associated_miR-34a-5p_Per2_signaling_docx/33718291 CC BY 4.0