Abstract

Introduction: Bone marrow transplantation is a critical approach for the treatment of many hematological disorders. Success of this approach is dependent on many factors the most important of which is the number of hematopoietic stem cells along with an efficient stroma. Co-transplantation of efficient mesenchymal stem cells can greatly improve the outcome of transplantations. Current researches assign a critical role for hypoxia inducible factor (HIF)-1 alpha in protection of various cells and tissues probably through induction of cytokines. To make this feature applicable to human bone marrow-derived mesenchymal stem cells, we manipulated these cells to over express HIF-1 alpha gene. Materials and methods: Full-length cDNA of human HIF-1 alpha was inserted into human bone marrow mesenchymal stem cells by pcDNA. 3.1 non-viral plasmid vector, and the effect of this over expression on production of some hematopoietic growth factors was explored. Moreover, using a co-culture system, the interactive impact of HIF-1 alpha-overexpressed mesenchymal stem cells on hematopoietic stem cells was evaluated. Results: Over expression of HIF-1 alpha in mesenchymal stem cells in normoxia increased production of one of the most important hematopoietic growth factors, Stem cell factor (also known as Steel factor or c-kit ligand). HIF1 alpha overexpression had no effect on production of other hematopoietic growth factors. In co-culture of mesenchymal stem cells-HIF-1 alpha with hematopoietic stem cells, enhancement of colony formation and reduced differentiation of hematopoietic stem cells were observed. Conclusion: Over expression of HIF-1 alpha in human bone marrow-derived mesenchymal stem cells can augment the production of some hematopoietic growth factors, and we suggest this response of mesenchymal stem cells could help to improve the outcome of bone marrow transplantation.