Effect of mesenchymal stem cell transplantation on the engraftment of human hematopoietic stem cells and leukemic cells in mice model

Abstract

We investigated the effect of human bone marrow-derived mesenchymal stem cells on engraftment of human umbilical cord blood CD34+ cells and acute myelogenous leukemia cells and also assessed the homing capability of MSCs. Forty-two NOD/SCID mice were administered sublethal irradiation followed by various cell doses of intravenous UCB CD34+ cells with or without MSCs. Another 12 NOD/SCID mice were also sublethally irradiated followed by intravenous injection of AML cells with or without MSCs. In ten of these mice, MSCs were genetically modified with an adenoviral vector encoding eGFP gene for tracking purpose. Cotransplantation of UCB CD34+)cells and MSCs resulted in a significant increase in bone marrow engraftment after 6 weeks, and the engraftment promoting effect of MSCs was proportional to the dose of MSCs and obvious when low doses of UCB CD34+ cells were given. There was no effect of MSCs on AML cells engraftment. All of the ten mice transplanted with eGFP-transfected MSCs showed positive for eGFP in their major organs. These data demonstrate that MSCs promote engraftment of UCB CD34+ cells in bone marrow, but exert no effect on engraftment of AML cells, and are capable of homing to the major organs including bone marrow following intravenous infusion.