Year 3

Over the course of this award we had made great progress working on all seven Milestones. We developed a protocol for EHM production under GLP conditions and completed the transplantation of EHM patches prepared from allogeneic and autologous non-human primate (NHP) cell lines. We also completed the transplantation of an allogeneic human size relevant patch format that did not cause any adverse effect on the recipient animals and had evidence of engraftment even afer six months. In addition we also tested different immunosuppression regimens to demonstrate the feasibility and safety of the NHP EHM construct as well as the transplantation procedure. We have harvested the heart explants with the transplanted grafts as well as other organs from all transplanted animals and performed histological analysis to determine the effect of different immunosuppression regimens on graft survival and cell proliferation in vivo. Data obtained from the allogeneic and autologous transplantation models helped us identify a suitable immunosuppression regimen that allows cell survival and engraftment for up to the total duration of the studies (6 months). Finally, with the resources and technology developed from this award, it paved the way to carry out IND enabling studies for obtaining approval for FIH clinical trial using these engineered heart tissue constructs.