title: Bone marrow mesenchymal stem cells overexpressing human basic fibroblast growth factor increase vasculogenesis in ischemic rats.
abstract: Administration or expression of growth factors, as well as implantation of autologous bone marrow cells, promote in vivo angiogenesis. This study investigated the angiogenic potential of combining both approaches through the allogenic transplantation of bone marrow-derived mesenchymal stem cells (MSCs) expressing human basic fibroblast growth factor (hbFGF). After establishing a hind limb ischemia model in Sprague Dawley rats, the animals were randomly divided into four treatment groups: MSCs expressing green fluorescent protein (GFP-MSC), MSCs expressing hbFGF (hbFGF-MSC), MSC controls, and phosphate-buffered saline (PBS) controls. After 2 weeks, MSC survival and differentiation, hbFGF and vascular endothelial growth factor (VEGF) expression, and microvessel density of ischemic muscles were determined. Stable hbFGF expression was observed in the hbFGF-MSC group after 2 weeks. More hbFGF-MSCs than GFP-MSCs survived and differentiated into vascular endothelial cells (P<0.001); however, their differentiation rates were similar. Moreover, allogenic transplantation of hbFGF-MSCs increased VEGF expression (P=0.008) and microvessel density (P<0.001). Transplantation of hbFGF-expressing MSCs promoted angiogenesis in an in vivo hind limb ischemia model by increasing the survival of transplanted cells that subsequently differentiated into vascular endothelial cells. This study showed the therapeutic potential of combining cell-based therapy with gene therapy to treat ischemic disease.
authors.affiliation: Department of Vascular Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.
authors.forename: J C
authors.initials: JC
authors.lastname: Zhang
authors.affiliation: Department of Vascular Surgery, The People's Hospital of Ganzhou, Ganzhou, China.
authors.forename: G F
authors.initials: GF
authors.lastname: Zheng
authors.affiliation: Department of Vascular Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.
authors.forename: L
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Vascular Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.
authors.forename: L Y
authors.initials: LY
authors.lastname: Ou Yang
authors.affiliation: Department of Vascular Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.
authors.forename: W X
authors.initials: WX
authors.lastname: Li
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000032:analysis; D001854:Bone Marrow Cells / Q000378:metabolism; D002454:Cell Differentiation; D004195:Disease Models, Animal; D005121:Extremities / Q000098:blood supply*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D015870:Gene Expression; D049452:Green Fluorescent Proteins; D006801:Humans; D007511:Ischemia / Q000503:physiopathology* / Q000628:therapy; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000098:blood supply; D018919:Neovascularization, Physiologic / Q000502:physiology*; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D014184:Transplantation, Homologous; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D000954:Antigens, Surface; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D049452:Green Fluorescent Proteins