Survival and Graft versus Host Disease in Murine MHC Mismatched Hematopoietic Stem Cell Transplantation with Co-injection of Mesenchymal Stem Cells

ABSTRACT

BACKGROUND: Intravenous injection of mesenchymal and hematopoietic stem cells (MSCs, HSCs) has the disadvantages of low delivery rate to bone marrow and sequestration of cells in the lung and liver. This study was designed to determine whether there is a relationship between the administration route and dosage of stem cells and GVHD and survival. METHODS: MSCs were retrieved from five subcultured C3H/10T1/2, cell lines from C3H/He mice. HSCs were transplanted by injecting 1 x 10(7) of bone marrow mononuclear cells and 5 x 10(6) of spleen cells from six to eight week old female C3H/He mice into six week old irradiated female BALB/c mice. The groups were divided into intravenous injection (IV) and intra-marrow (IM) injection groups. IV and IM+MSC groups consisted of mice transplanted with the same bone marrow mononuclear cells and SP, IV and IM groups, with the additional co-injection of 1 x 10(6) MSCs. RESULTS: Evaluation of all mice, in both groups, showed no difference in GVHD and survival. However, high dose injection with 1 x 10(6) MSCs led to a decreased incidence of GVHD (P<0.05) and improved survival (P<0.01) in both groups. CONCLUSION: The results of this study showed that the positive effects of MSC on GVHD and survival were primarily dependent on the number of injected cells.