Cardiovascular diseases remain the number one cause of death in the western world. Human embryonic stem cells (hESCs) represent a promising source of cells for the treatment of cardiovascular diseases because of their unlimited cell propagation and ability to give rise to different cell types, including cardiomyocytes, endothelial and smooth muscle cells. Cardiomyocytes isolated from hESCs have been shown to form new myocardium after infarct; however, the functional recovery of the myocardium was low and the functional coupling was inexistent since the cardiomyocytes were observed within the scar and not in direct contact with host cardiomyocytes (Laflamme et al., Nat Biotechnol 2007). So far, no studies have reported the benefits of prevascularizing cardiomyocyte cell constructs to enhance in vivo cell viability, grafting and functional coupling. Additionally, we anticipate that the transplantation of these cells using an injectable bioactive gel will enhance cell retention and viability at the injection site. This projects aims at evaluating the neovascularization and myocardium functional recovery after transplanting hESC-derived cardiomyocytes and vascular cells into a myocardial infarction animal model. Recently, we isolated endothelial and smooth muscle cells from hESCs that form microvessels when injected subcutaneously in nude mice and thus might be an important cell source for the vascularization of the myocardium. In addition, this projects aims at developing a bioactive injectable gel to function as a temporary three-dimensional scaffold and a protocol to monitor non-invasively in vivo cell grafting.
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