Laboratory of Cardiovascular Cell Biology, Department of Cell and Chemical Biology, Leiden University Medical Centre, Leiden, The Netherlands.
Laboratory of Experimental Cardiology, University Medical Center Utrecht, University Utrecht, Utrecht, The Netherlands.
J Cardiovasc Transl Res. 2019 Feb;12(1):5-17. doi: 10.1007/s12265-018-9842-9. Epub 2018 Nov 19.
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.
细胞移植研究表明，注射祖细胞可改善心肌梗死后的心脏功能。移植人心肌祖细胞（hCPCs）可提高射血分数，但存活率和整合率较低。因此，旁分泌因子（包括细胞外囊泡[EVs]）可能有助于发挥有益作用。我们通过移植 EV 分泌减少的 hCPCs 来研究 EV 的作用。有趣的是，这些 hCPCs 无法减少 MI 后的梗死面积。此外，注射 hCPC-EVs 可显著减少梗死面积。对 EV 摄取的分析显示，心肌细胞和内皮细胞呈阳性，这些细胞类型中的 Ki67 表达更高。与 Ki67 相关的增殖标志物 Yes 相关蛋白（YAP）在整个梗死区也增加。总之，我们的数据表明，EV 分泌是 hCPC 移植对 MI 后心脏恢复的短期有益作用的驱动力。
