Brief background of the proposal and its relevance to the CDI’s objectives
Pediatric dilated cardiomyopathy (DCM) is an important cause of mortality and is the most common indication for heart transplantation in children. There is a clinically unmet need to identify therapies for childhood heart failure. Distinct primitive (CCR2-) and definitive (CCR2+) macrophage populations contribute to cardiac repair and heart failure progression, respectively. This project proposes that CCR2- macrophages derived from human pluripotent stem cells (hPSC) may serve as a cell-based therapeutic for pediatric DCM.
Proposed specific aims
· Test the hypothesis that primitive and definitive hPSC-derived macrophages represent functionally distinct subsets with differing reparative and inflammatory potential.
· Define the requirements for primitive and definitive macrophage specification for regenerative medicine applications.
· Test the hypothesis that transplantation of hPSC-derived CCR2- macrophages is sufficient to augment tissue repair and functional recovery of the failing pediatric heart in a mouse model.
Potential impact on child health
The proposed studies will provide important and novel insights into whether hPSC-derived macrophages could serve as a cell-based therapeutic to promote tissue repair and functional recovery of the failing pediatric heart.