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Extracellular Vesicles Derived from Endothelial Progenitor Cells Modified by Houshiheisan Promote Angiogenesis and Attenuate Cerebral Ischemic Injury Via MiR-126/PIK3R2

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Journal Sci Rep
Specialty Science
Date 2024 Nov 15
PMID 39548169
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Abstract

Angiogenesis following cerebral ischemia is crucial for restoring blood supply to the ischemic region. Extracellular vesicles (EVs) derived from endothelial progenitor cells (EPCs) offer potential therapeutic benefits in the treatment of cerebral ischemia. Houshiheisan (HSHS) has been shown to improve clinical outcomes in ischemic stroke patients, reduce cerebral ischemic damage in rats, and protect endothelial cells. However, the potential effects of HSHS-modified EPC-derived EVs (EVs) for cerebral ischemia remain unexplored. This study investigated the impact of EVs on angiogenesis using rats with permanent middle cerebral artery occlusion (pMCAO) and brain microvascular endothelial cells (BMECs) subjected to oxygen-glucose deprivation (OGD). Results demonstrated that EVs promoted the proliferation, migration, and tube formation of BMECs in vitro. In vivo, high doses of EVs exhibited better performance than equivalent doses of unmodified EPC-derived EVs in reducing cerebral infarction volume, improving cortical blood perfusion, decreasing neurological deficit scores, and increasing cortical microvessel density at day 7 post-modeling. The pro-angiogenic effects of EVs following cerebral ischemia were associated with the regulation of miR-126 and the PIK3R2/PI3K/AKT pathway.

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