Blockade of TSP-1/CD47 signal axis promotes donor hematopoietic engraftment by improving SEC/MK niche function.

ABSTRACT: Thrombospondin-1 (TSP-1)/CD47 signaling induces cell death and inhibits angiogenesis. Here, we investigated the possibility of improving donor engraftment by blocking the TSP-1/CD47 pathway in mouse models of total body irradiation (TBI)-conditioned syngeneic hematopoietic stem cell transplantation (HSCT). Our findings revealed that HSCT engraftment was improved in mice deficient in CD47 (Cd47 ^-/- ) or TSP-1 (Thbs1 ^-/- ) compared to wild-type (WT) mice. The lack of TSP-1 or CD47 enhanced the production of CXCL12 by megakaryocytes and platelets, promoting the seeding of donor hematopoietic stem cells (HSCs) in sinusoidal endothelial cell (SEC)/megakaryocyte niches. Both Cd47 ^-/- and Thbs1 ^-/-

SUBMITTER: Wang F 

PROVIDER: S-EPMC11889568 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature