Lack of thrombospondin-2 reduces fibrosis and increases vascularity around cardiac cell grafts

Background is around cardiac cell injections represents an obstacle to graft integration in cell-based cardiac repair. Thrombospondin-2 (TSP-2) is a pro-fibrotic, anti-angiogenic matricellular protein and an attractive target for therapeutic knockdown to improve cardiac graft integration and survival. s d a TSP-2 knockout (KO) mouse in conjunction with a fetal murine cardiomyocyte grafting model to evaluate the effects of a lack of TSP-2 on fibrosis, vascular density, and graft size in the heart. s eks after grafting in the uninjured heart, fibrosis area was reduced 4.5-fold in TSP-2 KO mice, and the thickness of the peri-graft scar capsule was reduced sevenfold compared to wild-type (WT). Endothelial cell density in the peri-graft region increased 2.5-fold in the absence of TSP-2, and cardiomyocyte graft size increased by 46% in TSP-2 KO hearts. sions is a key regulator of fibrosis and angiogenesis following cell grafting in the heart, and its absence promotes better graft integration, vascularization, and survival. y is around cardiac cell injections impairs graft integration in cell-based cardiac repair. TSP-2 is a pro-fibrotic, anti-angiogenic matricellular protein. Using a TSP-2-knockout mouse model and cardiac cell transplantation, we found significantly reduced fibrosis and increased endothelial cell density in the peri-graft region. Thus, TSP-2 is an attractive target for therapeutic knockdown to improve cardiac graft integration and survival.