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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 (PBL) and platelets was accelerated when CXCR4-MSCs were co-transplanted with BM cells.The frequency of c-kit+Sca+Lin-(KSL) 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 ofhematopoietic recovery and sustained hematopoiesis.