Extracellular vesicles engineering by silicates-activated endothelial progenitor cells for myocardial infarction treatment in male mice

Bin Yu, Hekai Li, Zhaowenbin Zhang, Peier Chen, Ling Wang, Xianglin Fan, Xiaodong Ning, Yuxuan Pan, Feiran Zhou, Xinyi Hu, Jiang Chang () and Caiwen Ou ()
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Bin Yu: Guangdong Provincial Key Laboratory of Cardiac Function and Microcirculation
Hekai Li: Zhujiang Hospital, Guangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular Disease, Southern Medical University
Zhaowenbin Zhang: Wenzhou Institute, Zhejiang Engineering Research Center for Tissue Repair Materials, University of Chinese Academy of Sciences
Peier Chen: Zhujiang Hospital, Guangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular Disease, Southern Medical University
Ling Wang: Southern Medical University
Xianglin Fan: Zhujiang Hospital, Guangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular Disease, Southern Medical University
Xiaodong Ning: Guangdong Provincial Key Laboratory of Cardiac Function and Microcirculation
Yuxuan Pan: Guangdong Provincial Key Laboratory of Cardiac Function and Microcirculation
Feiran Zhou: Zhujiang Hospital, Guangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular Disease, Southern Medical University
Xinyi Hu: Zhujiang Hospital, Guangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular Disease, Southern Medical University
Jiang Chang: Guangdong Provincial Key Laboratory of Cardiac Function and Microcirculation
Caiwen Ou: Guangdong Provincial Key Laboratory of Cardiac Function and Microcirculation

Nature Communications, 2023, vol. 14, issue 1, 1-21

Abstract: Abstract Extracellular vesicles have shown good potential in disease treatments including ischemic injury such as myocardial infarction. However, the efficient production of highly active extracellular vesicles is one of the critical limitations for their clinical applications. Here, we demonstrate a biomaterial-based approach to prepare high amounts of extracellular vesicles with high bioactivity from endothelial progenitor cells (EPCs) by stimulation with silicate ions derived from bioactive silicate ceramics. We further show that hydrogel microspheres containing engineered extracellular vesicles are highly effective in the treatment of myocardial infarction in male mice by significantly enhancing angiogenesis. This therapeutic effect is attributed to significantly enhanced revascularization by the high content of miR-126a-3p and angiogenic factors such as VEGF and SDF-1, CXCR4 and eNOS in engineered extracellular vesicles, which not only activate endothelial cells but also recruit EPCs from the circulatory system.

Date: 2023
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DOI: 10.1038/s41467-023-37832-y

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