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

Feng Wang; Yan-Hou Liu; Ting Zhang; Xintong Hou; Yanbao Xin; Guang-Yao Xie; Wen-Jie Zhao; Xue Wang; Tianmeng Sun; Zheng Hu; Yong-Guang Yang

doi:10.1016/j.isci.2025.111952

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

iScience. 2025 Feb 4;28(3):111952. doi: 10.1016/j.isci.2025.111952. eCollection 2025 Mar 21.

Authors

Feng Wang^{1

2}, Yan-Hou Liu^{1

2}, Ting Zhang^{1

2}, Xintong Hou^{1

2}, Yanbao Xin^{1

2}, Guang-Yao Xie^{1

2}, Wen-Jie Zhao^{1

2}, Xue Wang^{1

2}, Tianmeng Sun^{1

2

3}, Zheng Hu^{1

2}, Yong-Guang Yang^{1

2

3}

Affiliations

¹ Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, The First Hospital, and Institute of Immunology, Jilin University, Changchun, China.
² National-local Joint Engineering Laboratory of Animal Models for Human Diseases, Changchun, China.
³ International Center of Future Science, Jilin University, Changchun, Jilin, China.

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 ^-/- mice showed reduced platelet adhesion to sinusoidal vascular cells, attenuated endothelial injury, and enhanced BM vascular regeneration, preserving SEC niches. Antibody neutralization of TSP-1 significantly increased CXCL12 production, donor HSC engraftment, and vascular niche regeneration in WT mice. In summary, the TSP-1/CD47 pathway is a promising therapeutic target to enhance HSCT efficacy and reduce endothelial injury syndrome.

Keywords: Biological sciences; Cell biology; Stem cells research.