Human Pericardial Fluid-Derived Cells Exhibit Mesothelial-like Properties and Exert Proangiogenic Effects on...

Modern therapies aimed at stimulating heart vascularization are critical for regenerating damaged heart tissue and treating ischemic heart disease. Approaches based on developmental biology concepts, particularly those involving the use of cells to coordinate vascular network formation, are of great interest. In this context, epicardial mesothelial cells (MCs) have emerged as a key regulator of blood and lymphatic vessel development during cardiogenesis. However, therapeutic targeting of MCs remains challenging because of anatomical constraints and the difficulties related to isolation of viable cell cultures for research. In this study, we demonstrate for the first time that the pericardial fluid contains cell layers, being an easily accessible source of cardiac MCs. These cells exhibit a characteristic epithelial-like morphology and robust in vitro proliferation, and an ability to undergo epicardial-to-mesenchymal transition in response to TGFβ1. They secrete a broad range of proangiogenic and proinflammatory factors and exert a potent effect on endothelial cells, stimulating proangiogenic behavior and promoting vascular structure formation on Matrigel^TM. Treating MCs with TGF-β1 enhances the secretion of VEGF, G-CSF, GM-CSF and MCP-3, thereby boosting their proangiogenic properties. Therefore, pericardial fluid is an easily accessible source of MCs for studying their regulatory mechanisms, for being applied in tissue engineering, and for developing approaches to improve heart vascularization.