Cardiac Progenitor Cell-Derived Extracellular Vesicles Reduce Infarct Size and Associate with Increased Cardiovascular Cell Proliferation.

Autor: Maring JA; Laboratory of Cardiovascular Cell Biology, Department of Cell and Chemical Biology, Leiden University Medical Centre, Leiden, The Netherlands., Lodder K; Laboratory of Cardiovascular Cell Biology, Department of Cell and Chemical Biology, Leiden University Medical Centre, Leiden, The Netherlands., Mol E; Laboratory of Experimental Cardiology, University Medical Center Utrecht, University Utrecht, Utrecht, The Netherlands., Verhage V; Laboratory of Experimental Cardiology, University Medical Center Utrecht, University Utrecht, Utrecht, The Netherlands., Wiesmeijer KC; Laboratory of Cardiovascular Cell Biology, Department of Cell and Chemical Biology, Leiden University Medical Centre, Leiden, The Netherlands., Dingenouts CKE; Laboratory of Cardiovascular Cell Biology, Department of Cell and Chemical Biology, Leiden University Medical Centre, Leiden, The Netherlands., Moerkamp AT; Laboratory of Cardiovascular Cell Biology, Department of Cell and Chemical Biology, Leiden University Medical Centre, Leiden, The Netherlands., Deddens JC; Laboratory of Experimental Cardiology, University Medical Center Utrecht, University Utrecht, Utrecht, The Netherlands., Vader P; Laboratory of Experimental Cardiology, University Medical Center Utrecht, University Utrecht, Utrecht, The Netherlands.; Department of Clinical Chemistry and Hematology, University Medical Center Utrecht, Utrecht, The Netherlands., Smits AM; Laboratory of Cardiovascular Cell Biology, Department of Cell and Chemical Biology, Leiden University Medical Centre, Leiden, The Netherlands., Sluijter JPG; Laboratory of Experimental Cardiology, University Medical Center Utrecht, University Utrecht, Utrecht, The Netherlands.; UMC Utrecht Regenerative Medicine Center, University Medical Center Utrecht, Utrecht, The Netherlands., Goumans MJ; Laboratory of Cardiovascular Cell Biology, Department of Cell and Chemical Biology, Leiden University Medical Centre, Leiden, The Netherlands. m.j.goumans@lumc.nl.
Jazyk: angličtina
Zdroj: Journal of cardiovascular translational research [J Cardiovasc Transl Res] 2019 Feb; Vol. 12 (1), pp. 5-17. Date of Electronic Publication: 2018 Nov 19.
DOI: 10.1007/s12265-018-9842-9
Abstrakt: 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.
Databáze: MEDLINE
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