Host-Dependent Vascularization in Cardiac Tissue Engineering

Abstract

Cardiac tissue engineering could address the growing need for donor hearts by supplying an alternative source of human myocardium. However, vascularization remains a barrier to clinical translation of this technology. While a variety of strategies have been developed to vascularize engineered tissues, it is not known whether these methods can be successfully applied across different host contexts. In this thesis, we use a previously developed method of guiding vascularization with patterned endothelial “cords” to study the integration of artificial tissues across implant locations and species. First, we describe an aberrant host response to guided vascularization in the athymic rat heart. Instead of finding patterned vasculature as has been previously reported, we found loss of patterning and robust inflammation. To investigate the host factors that could explain these results, we next compared the response to artificial patches implanted in different implant sites (IP and heart) and species (mouse and rat). Comparison of responses to artificial tissues between athymic mice and athymic rats revealed host differences in inflammation, cardiomyocyte engraftment, and vascularization. These results demonstrate the critical importance of host biology to the integration of engineered tissues. Future work is needed to understand and optimize specific host factors that control vascularization and tissue engraftment.