Given their self-renewing and pluripotent capabilities, embryonic stem cells (ESCs) are well-poised as a cellular source for tissue regeneration therapy. Successful in vitro differentiation of both mouse (m) and human (h) ESCs into multiple somatic cell types has been reported, including cardiomyocytes, neurons and pancreatic islet cells. However, the host immune response against transplanted ESCs is not well characterized. In fact, controversy remains as to whether ESCs have immune-privileged properties. The scope of the current thesis is to gain insight into immunological aspects of transplantation of embryonic stem cells or their differentiated progeny by using molecular imaging techniques to follow cell fate. Specifically, this thesis presents evidence that: (1) molecular imaging can be used to quantify organ and ESC survival following transplantation and non-invasively follow donor graft fate; (2) ESCs express MHC and co-signaling molecules that are upregulated upon differentiation; (3) mESCs and hESCs can trigger potent cellular and humoral immune responses following allogeneic and/or xenogeneic transplantation, leading to rejection; and (4) immunosuppressive drugs can significantly mitigate the host immune response to prolong hESC survival in immunocompetent mice. These results clearly indicate that ESC immunogenicity is a significant hurdle that must be overcome before successful clinical application can be accomplished.UBL - phd migration 201
