In Vitro Generation of Cardiovascular Tissues

Cardiovascular diseases are leading causes of mortality and morbidity. New cell‐based therapies offer new strategies in treating these disorders. We have focused on using a collagen tube cell scaffold on which cardiovascular tissues can be grown and manipulated. This scaffold has been used to investigate cardiac myocytes (CMs), cardiac valves, and coronary vessel development. Spontaneously contracting CMs have been cultured for months on the tubular scaffold without dedifferentiation or fibroblast overgrowth. This attribute was used to study valve formation. These studies found that valve leaflet formation was dependent on the presence of CMs. We are investigating if the role that CMs play in the valve forming process is that of a source of juxacrine signals or as generators of critical fluid flow or both. The role CMs play in the formation of coronary vasculature has also been tested in this system. Our data indicate that CMs significantly enhanced endothelial and smooth muscle cell proliferation. Vessel formation was also increased in co‐cultures of CMs and proepicardial cells (coronary vascular precursors). Mechanistic investigations of this process are underway. Again, the properties of the tube scaffold are used to investigate both chemical and mechanical components. The generation these cardiovascular tissues in vitro allows for the investigation of the developmental mechanisms that drive morphogenesis. Understanding these mechanisms enables the rational use of cell‐based therapies.