期刊
MATERIALS TODAY BIO
卷 12, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.mtbio.2021.100171
关键词
Hypoxia inducible factor-1 alpha; Extracellular Vesicles; Mesenchymal stem cells; myocardial infarction
资金
- Changzhou SciTech Program [CJ20210059]
- Young Talent Development Plan of Changzhou Health Commission [CZQM2020060]
- National Natural Science Foundation of China [81901410]
- Sci&Tech development fund of Nanjing Medical University [NMUB2020069]
- Major Research Plan of Changzhou Health Commission [ZD202020]
EVs derived from HIF-1α-engineered MSCs can promote angiogenesis of endothelial cells and apoptosis of cardiomyocytes through upregulating the expression of miR-221-3p. Additionally, RGD hydrogels can enhance the therapeutic efficacy of these EVs.
Aims: Naturally secreted extracellular vesicles (EVs) play important roles in stem-mediated cardioprotection. This study aimed to investigate the cardioprotective function and underlying mechanisms of EVs derived from HIF-1 alpha engineered mesenchymal stem cells (MSCs) in a rat model of AMI. Methods and results: EVs isolated from HIF-1 alpha engineered MSCs (HIF-1 alpha-EVs) and control MSCs (NC-EVs) were prepared. In in vitro experiments, the EVs were incubated with cardiomyocytes and endothelial cells exposed to hypoxia and serum deprivation (H/SD); in in vivo experiments, the EVs were injected in the acutely infarcted hearts of Sprague-Dawley rats. Compared with NC-EVs, HIF-1 alpha-EVs significantly inhibited the apoptosis of cardiomyocytes and enhanced angiogenesis of endothelial cells; meanwhile, HIF-1 alpha-EVs also significantly shrunk fibrotic area and strengthened cardiac function in infarcted rats. After treatment with EVs/RGD-biotin hydrogels, we observed longer retention, higher stability in HIF-1 alpha-EVs, and stronger cardiac function in the rats. Quantitative real-time PCR (qRT-PCR) displayed that miRNA-221-3p was highly expressed in HIF-1 alpha-EVs. After miR-221-3p was inhibited in HIF-1 alpha-EVs, the biological effects of HIF-1 alpha EVs on apoptosis and angiogenesis were attenuated. Conclusion EVs released by MSCs with HIF-1 alpha overexpression can promote the angiogenesis of endothelial cells and the apoptosis of cardiomyocytes via upregulating the expression of miR-221-3p. RGD hydrogels can enhance the therapeutic efficacy of HIF-1 alpha engineered MSCs-derived EVs.
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