Journal article
Extracellular vesicles from human embryonic stem cell-derived cardiovascular progenitor cells promote cardiac infarct healing through reducing cardiomyocyte death and promoting angiogenesis
Cell death & disease, Vol.11(5), pp.354-354
05/11/2020
DOI: 10.1038/s41419-020-2508-y
PMCID: 7214429
PMID: 32393784
Abstract
Human pluripotent stem cells (hPSCs)-derived cardiovascular progenitor cells (CVPCs) are a promising source for myocardial repair, while the mechanisms remain largely unknown. Extracellular vesicles (EVs) are known to mediate cell-cell communication, however, the efficacy and mechanisms of hPSC-CVPC-secreted EVs (hCVPC-EVs) in the infarct healing when given at the acute phase of myocardial infarction (MI) are unknown. Here, we report the cardioprotective effects of the EVs secreted from hESC-CVPCs under normoxic (EV-N) and hypoxic (EV-H) conditions in the infarcted heart and the long noncoding RNA (lncRNA)-related mechanisms. The hCVPC-EVs were confirmed by electron microscopy, nanoparticle tracking, and immunoblotting analysis. Injection of hCVPC-EVs into acutely infracted murine myocardium significantly improved cardiac function and reduced fibrosis at day 28 post MI, accompanied with the improved vascularization and cardiomyocyte survival at border zones. Consistently, hCVPC-EVs enhanced the tube formation and migration of human umbilical vein endothelial cells (HUVECs), improved the cell viability, and attenuated the lactate dehydrogenase release of neonatal rat cardiomyocytes (NRCMs) with oxygen glucose deprivation (OGD) injury. Moreover, the improvement of the EV-H in cardiomyocyte survival and tube formation of HUVECs was significantly better than these in the EV-N. RNA-seq analysis revealed a high abundance of the lncRNA MALAT1 in the EV-H. Its abundance was upregulated in the infarcted myocardium and cardiomyocytes treated with hCVPC-EVs. Overexpression of human MALAT1 improved the cell viability of NRCM with OGD injury, while knockdown of MALAT1 inhibited the hCVPC-EV-promoted tube formation of HUVECs. Furthermore, luciferase activity assay, RNA pull-down, and manipulation of miR-497 levels showed that MALAT1 improved NRCMs survival and HUVEC tube formation through targeting miR-497. These results reveal that hCVPC-EVs promote the infarct healing through improvement of cardiomyocyte survival and angiogenesis. The cardioprotective effects of hCVPC-EVs can be enhanced by hypoxia-conditioning of hCVPCs and are partially contributed by MALAT1 via targeting the miRNA.
Details
- Title: Subtitle
- Extracellular vesicles from human embryonic stem cell-derived cardiovascular progenitor cells promote cardiac infarct healing through reducing cardiomyocyte death and promoting angiogenesis
- Creators
- Qiang Wu - Shanghai Institute of Nutrition and HealthJinxi Wang - Shanghai Institute of Nutrition and HealthWilson Lek Wen Tan - National University of SingaporeYun Jiang - Shanghai Institute of Nutrition and HealthShihui Wang - Shanghai Institute of Nutrition and HealthQiang Li - Shanghai Institute of Nutrition and HealthXiujian Yu - Shanghai Institute of Nutrition and HealthJiliang Tan - Shanghai Institute of Nutrition and HealthShenyan Liu - Shanghai Institute of Nutrition and HealthPeng Zhang - Shanghai Institute of Nutrition and HealthZenia Tiang - National University of SingaporeZhongyan Chen - Shanghai Institute of Nutrition and HealthRoger Sik-Yin Foo - National University of SingaporeHuang-Tian Yang - Shanghai Institute of Nutrition and Health
- Resource Type
- Journal article
- Publication Details
- Cell death & disease, Vol.11(5), pp.354-354
- DOI
- 10.1038/s41419-020-2508-y
- PMID
- 32393784
- PMCID
- 7214429
- NLM abbreviation
- Cell Death Dis
- ISSN
- 2041-4889
- eISSN
- 2041-4889
- Publisher
- Springer Nature
- Number of pages
- 16
- Grant note
- XDA16010201 / Strategic Priority Research Program of the Chinese Academy of Sciences; Chinese Academy of Sciences 2017YFA0103700; 2016YFC1301204 / National Key R&D Program of China 81520108004; 81470422 / National Natural Science Foundation of China; National Natural Science Foundation of China (NSFC)
- Language
- English
- Date published
- 05/11/2020
- Academic Unit
- Internal Medicine
- Record Identifier
- 9984446554902771
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