P112Epithelial-to-mesenchymal transition is required for a therapeutic effect of epicardial-derived cells after myocardial infarction

Funding Acknowledgements: This study is funded by The Netherlands Organization for Scientific Research (NWO) VENI and a LUMC Research fellowship Introduction: The cells of the epicardium -the epithelial layer covering the outside of the heart-, are activated after ischemic injury. Upon damage these cells undergo epithelial-to mesenchymal-transition (EMT). The epicardial-derived cells (EPDCs) contribute to repair either via migration and differentiation, or via a paracrine mechanism. Previous research revealed that direct transplantation of cultured human mesenchymal EPDCs into the infarcted mouse heart attenuated remodelling, increased vascularisation and improved cardiac function. We recently developed a cell culture protocol for human EPDCs in their cobblestone-like epithelial state (cEPDCs) allowing us to compare EPDCs prior to and post-EMT. cEPDCs are more plastic with the ability to differentiate into a range of mesenchymal cell types including smooth muscle cells, cardiac fibroblasts, and possibly to cardiomyocytes and endothelial cells. Therefore, we questioned whether cEPDCs have a better therapeutic potential compared to mesenchymal spindle-shaped EPDCs (sEPDCs) after myocardial infarction (MI).