The role of mesenchymal stem cells in hematopoietic stem cell transplantation / 대한내과학회지

ABSTRACT

BACKGROUND: Human bone marrow contains mesenchymal stem cells (MSCs) which are capable of differentiation into a number of mesenchymal cell lineages when stimulated under appropriate conditions. Many studies indicate that the bone marrow stroma is damaged following bone marrow transplantation. Animal models suggest that the transplantation of healthy stromal elements, including MSCs, may enhance the ability of the bone marrow microenvironment to support hematopoiesis after stem cell transplantation. However, it remains to be seen whether transplantation of MSCs has significant value and pre-culture of hematopoietic stem cells with MSCs prior to transplantation changes their engraftment. METHODS: We investigated the differentiation potential and the potential plasticity of MSCs. And we also studied whether they have any effects on hematopoietic engraftment in xenotransplantation animal model. RESULTS: Culture-expanded human MSCs exhibited a spindle-shaped fibroblastic morphology and were differentiated into adipocytes, osteoblasts, and chondrocytes in specific culture conditions. In xenograft animal model, human ex vivo expanded marrow-derived MSCs were cotransplantated with human CD34+ cells into NOD/SCID mice and demonstrated about a two-fold increase in bone marrow engraftment as determined by human CD45+ and CD34+ expression as compared to transplantation of CD34+ cells alone. Also MSCs resulted in a two-fold to three-fold increase in bone marrow engraftment of CD45+- CD33+ cells and CD45+- CD13+ cells, whereas no such effect were observed in engraftment of CD45+- CD3+ cells and CD45+- CD19+ cells. To determine the homing and engraftment of MSCs, we performed cotransplantation of human CD34+ cells with ex vivo expanded human MSCs that had been retrovirally transduced with GFP transgene into NOD/SCID mice. Expression of GFP was found in the bone marrow of 1 of 5 NOD/SCID mice by DNA-PCR analysis. Using DNA-PCR, we found human beta2-microglobulin expression in liver, spleen, thymus, lung, heart, kidney, and small intestine. CONCLUSION: These results suggest that MSCs are capable of enhancing hematopoietic engraftment and they also may possess therapeutic value for the repair of damaged mesenchymal tissues following hematopoietic stem cell transplantation.