title: Over expression of HIF-1α in human mesenchymal stem cells increases their supportive functions for hematopoietic stem cells in an experimental co-culture model.
abstract: BACKGROUND
  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)-1α 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-1α gene.
  
  
  METHODS
  Full-length cDNA of human HIF-1α 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-1α-overexpressed mesenchymal stem cells on hematopoietic stem cells was evaluated. Results Over expression of HIF-1α 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). HIF-1α overexpression had no effect on production of other hematopoietic growth factors. In co-culture of mesenchymal stem cells-HIF-1α with hematopoietic stem cells, enhancement of colony formation and reduced differentiation of hematopoietic stem cells were observed. Conclusion Over expression of HIF-1α 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.
authors.forename: Ali Asghar
authors.initials: AA
authors.lastname: Kiani
authors.forename: Jahangir
authors.initials: J
authors.lastname: Abdi
authors.forename: Rahele
authors.initials: R
authors.lastname: Halabian
authors.forename: Mehryar Habibi
authors.initials: MH
authors.lastname: Roudkenar
authors.forename: Naser
authors.initials: N
authors.lastname: Amirizadeh
authors.forename: Mohammad
authors.initials: M
authors.lastname: Soleiman Soltanpour
authors.forename: Ahmad
authors.initials: A
authors.lastname: Kazemi
mesh_terms: D016026:Bone Marrow Transplantation / Q000379:methods*; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D018920:Coculture Techniques; D018076:DNA, Complementary / Q000235:genetics / Q000378:metabolism; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis* / Q000235:genetics; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism*; D019089:Stem Cell Factor / Q000096:biosynthesis / Q000235:genetics; D014162:Transfection; D019172:Transplantation Conditioning / Q000379:methods
chemical_list: D018076:DNA, Complementary; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D019089:Stem Cell Factor
keywords: Co-culture; HIF-1α; Hematopoietic stem cells; Human mesenchymal stem cells; Stem cell factor