The Use of a Three‐Dimensional Model System to Study the Role of the Myocardium during Coronary Development

Congenital abnormalities during coronary development result in severe defects in cardiac function. Furthermore, coronary vessel disease is a leading cause of mortality and morbidity. A mechanistic understanding of coronary development would aid in the development of new therapies for both developmental and adult disorders. Here, we present an in vitro model system in which the mechanisms that regulate coronary vessel formation can be studied. This system uses a 3‐D scaffold on which developing cardiac tissues can be grown. Proepicardial (PE) cells, which form the coronary vasculature, were isolated from quail embryos and seeded on the 3‐D cell scaffold either with or without cardiac myocytes (CMs). Vessel‐like structures were observed regardless of the presence of CMs; however, they were more prevalent in CM co‐cultures. Cells of these vessels were positive for QH‐1, an endothelial cell (EC) marker, and ƒÑ‐smooth muscle actin, which is expressed as individual vessels mature. BrdU analysis found increases EC DNA synthesis when co‐cultured with CMs. It is hypothesized that paracrine factors secreted from the myocardium induce the proliferation of PE‐derived cells, thus promoting coronary development. Understanding the proliferative response of PE‐derived cells to CMs will allow for the examination of the specific role that the myocardium plays in the morphogenesis of the coronary vasculature.