EPC infusion ameliorates acute graft-versus-host disease-related endothelial injury after allogeneic bone marrow transplantation

Weiwei Wang; Yali Ye; Yuwei Du; Zhengqing Xu; Ke Yuan; Yizhou Wang; Seyram Yao Adzraku; Yue Li; Kailin Xu; Jianlin Qiao; Wen Ju; Lingyu Zeng

doi:10.3389/fimmu.2022.1019657

EPC infusion ameliorates acute graft-versus-host disease-related endothelial injury after allogeneic bone marrow transplantation

Front Immunol. 2022 Dec 14:13:1019657. doi: 10.3389/fimmu.2022.1019657. eCollection 2022.

Authors

Weiwei Wang^{1

2

3}, Yali Ye^{1

2

3}, Yuwei Du^{1

2

3}, Zhengqing Xu^{1

2

3}, Ke Yuan^{1

2

3}, Yizhou Wang^{1

2

3}, Seyram Yao Adzraku^{1

2

3}, Yue Li^{1

2

3}, Kailin Xu^{1

2

3}, Jianlin Qiao^{1

2

3}, Wen Ju^{1

2

3}, Lingyu Zeng^{1

2

3}

Affiliations

¹ Blood Diseases Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China.
² Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.
³ Jiangsu Key Laboratory of Bone Marrow Stem Cells, Xuzhou, Jiangsu, China.

Abstract

Introduction: Graft-versus-host disease (GVHD) damages vascular endothelium. Endothelial progenitor cell (EPC) can differentiate to endothelial cell and promote angiogenesis, but its role in endothelial damage in GVHD is unclear.

Methods: In this study, we intend to assess whether EPC infusion promotes the repair of endothelial injury in GVHD mouse model. Male BALB/c mice were randomly divided into 5 groups: control group, total body irradiation group (TBI group), allogeneic bone marrow transplantation group (Allo-BMT group), acute graft versus host disease group (GVHD group), EPC infusion group (GVHD+EPC group) followed by analysis of mice survival, acute GVHD (aGVHD) score, T cell infiltration by immunofluorescence, as well as continuity of vascular endothelium in liver.

Results: Compared with Allo-BMT group, the clinical and pathological score of aGVHD mice were higher. On day 21 after transplantation, a large number of mononuclear cell infiltrations were seen in the target tissues of aGVHD mice and mice died within 30 days. In addition, aGVHD group also presented increased subendothelial infiltration of CD3⁺ T cells in the liver, decreased VE-cadherin expression and elevated major histocompatibility complex (MHC) II molecule expression in the endothelium. Moreover, expression of MHC-II molecule increased in endothelial cell after irradiation injury and LPS stimulation, indicating abnormally activated endothelial cell with antigen-presenting function. Interestingly, infusion of EPC reduced the clinical and pathological score of aGVHD, decreased infiltration of mononuclear cells, improved survival as well as upregulated VE-cadherin and downregulated MHC-II molecule.

Discussion: EPC infusion can mobilize to affected endothelium to decrease the infiltration of T cells and pathological endothelial activation contributing to ameliorating the damage of endothelium. EPC infusion combined with bone marrow transplantation might be a perspective strategy for the prevention and treatment of aGVHD.

Keywords: acute graft-versus-host disease; endothelial cell activation; endothelial injury; endothelial progenitor cell; endothelium.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Bone Marrow Transplantation / adverse effects
Graft vs Host Disease* / prevention & control
Hematopoietic Stem Cell Transplantation*
Histocompatibility Antigens Class II
Male
Mice
Transplantation, Homologous

Substances

Histocompatibility Antigens Class II