Journal
JOURNAL OF CARDIOVASCULAR TRANSLATIONAL RESEARCH
Volume 12, Issue 1, Pages 5-17Publisher
SPRINGER
DOI: 10.1007/s12265-018-9842-9
Keywords
Extracellular vesicles; Cardiac progenitor cells; Myocardial infarction; Proliferation; Cardiomyocytes; Angiogenesis; Endoglin
Funding
- ZonMW-Translational Adult Stem cell research (TAS grant) [116002016]
- BioMedical Materials institute - Dutch Ministry of Economic Affairs, Agriculture and Innovation [P1.04SMARTCARE]
- Horizon2020 ERC-2016-COG EVICARE [725229]
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Cell transplantation studies have shown that injection of progenitor cells can improve cardiac function after myocardial infarction (MI). Transplantation of human cardiac progenitor cells (hCPCs) results in an increased ejection fraction, but survival and integration are low. Therefore, paracrine factors including extracellular vesicles (EVs) are likely to contribute to the beneficial effects. We investigated the contribution of EVs by transplanting hCPCs with reduced EV secretion. Interestingly, these hCPCs were unable to reduce infarct size post-MI. Moreover, injection of hCPC-EVs did significantly reduce infarct size. Analysis of EV uptake showed cardiomyocytes and endothelial cells primarily positive and a higher Ki67 expression in these cell types. Yes-associated protein (YAP), a proliferation marker associated with Ki67, was also increased in the entire infarcted area. In summary, our data suggest that EV secretion is the driving force behind the short-term beneficial effect of hCPC transplantation on cardiac recovery after MI.
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