Co-transplantation of Hematopoietic Stem Cells and Cxcr4 Gene-Transduced Mesenchymal Stem Cells Promotes Hematopoiesis.

Abstract

Mesenchymal stem cells (MSCs) are a promising candidate for cellular therapies. Co-transplantation of MSCs and hematopoietic stem cells (HSCs) promotes successful engraftment and improves hematopoietic recovery. In this study, the effects of co-transplantation of HSCs and mouse bone marrow (BM)-derived MSCs overexpressing CXCR4 (CXCR4-MSC) on CXCR4-MSC homing capacity and the reconstitution potential in lethally irradiated mice were evaluated. Recovery of donor-derived peripheral blood leukocytes and platelets was accelerated when CXCR4-MSCs were co-transplanted with BM cells. The frequency of c-kit(+)Sca(+)Lin(-) HSCs was higher in recipient BM following co-transplantation of CXCR4-MSCs compared with the EGFP-MSC control and the BMT only groups. Surprisingly, the rate of early engraftment of donor-derived BM cells in recipients co-transplanted with CXCR4-MSCs was slightly lower than in the absence of MSCs on day 7. Moreover, co-transplantation of CXCR4-MSCs regulated the balance of T helper cells subsets. Hematopoietic tissue reconstitution was evaluated by histopathological analysis of BM and spleen. Co-transplantation of CXCR4-MSCs was shown to promote the recovery of hematopoietic organs. These findings indicate that co-transplantation of CXCR4-MSCs promotes the early phase of hematopoietic recovery and sustained hematopoiesis.