Cotransplantation of human umbilical cord blood-derived stromal cells enhances hematopoietic reconstitution and engraftment in irradiated BABL/c mice

Abstract

Our previous study demonstrated that human umbilical cord blood-derived stromal cells (hUCBDSCs) support the growth of hematopoietic stem cells, and promote the expansion of colony-forming units of megakaryocyte (CFU-Mk) even more efficiently than human bone marrow stromal cells (hBMSCs). Given the unique role of hUCBDSCs in megakaryocytopoiesis in vitro, in this follow up study, we further investigated their effects in vivo on hematopoiesis in the setting of hematopoietic stem cell (HSC) transplants. After infusing hematopoietic cells alone or together with either hUCBDSCs or hBMSCs into lethally irradiated BABL/c mice, we examined the engraftment of human CD45+ cells in the mouse bone marrow with flow cytometry, observed the survival rate of irradiated mice, obtained blood counts and bone marrow biopsies at different time points post-transplant, and assessed colony forming and the homing efficiency of hematopoietic cells. By comparing HSC transplantation with or without stromal cells, we show here that hUCBDSCs efficiently promote the homing of hematopoietic cells to the marrow and enhance the engraftment after cotransplantation. They also promote hematopoietic reconstitution, particularly of the megakaryocytic lineage, and restore the impaired stromal microenvironment after radiation-induced damages. These effects of hUCBDSCs are more potent than those of hBMSCs. In conclusion, our findings suggest the role of hUCBDSCs to facilitate hematopoietic reconstitution and engraftment when cotransplanted with hematopoietic cells.