The protective effects of umbilical cord‐derived endothelial colony forming cells on hepatic veno‐occlusive disease

Abstract Hepatic veno‐occlusive disease (HVOD) characterized by endothelial cell dysfunction is one of the serious complications after hematopoietic stem‐cell transplantation or chemotherapeutic drug application. The mortality of HVOD patients with multiorgan dysfunction is as high as 80%. The primary aim of this study was to evaluate whether the infusion of human umbilical cord‐derived endothelial colony forming cells (hUC‐ECFCs) could mitigate HVOD injury and investigate the underlying mechanism. We found that the expression of chemokine C–X–C chemokine ligand 12 (CXCL12) was markedly increased in the livers of HVOD mice. Meanwhile, hUC‐ECFCs infusion could significantly ameliorate liver injury in HVOD mice, which was accompanied by hUC‐ECFCs recruitment in the liver, reduced liver pathological alterations, and decreased serum alanine aminotransferase and aspartate aminotransferase activity. Besides, CXCL12‐induced migration in hUC‐ECFCs was partly impeded by chemokine receptor type 7 (CXCR7) silence or CXCR4 blockage. In conclusion, our results demonstrated that hUC‐ECFCs could mitigate HVOD through homing to the injured liver via the CXCL12‐CXCR4/CXCR7 signaling pathway.