title: Low angiogenic potency induced by the implantation of ex vivo expanded CD117(+) stem cells.
abstract: Ex vivo expansion of stem cells might be a feasible method of resolving the problem of limited cell supply in cell-based therapy. The implantation of expanded CD34(+) endothelial progenitor cells has the capacity to induce angiogenesis. In this study, we tried to induce angiogenesis by implanting expanded CD117(+) stem cells derived from mouse bone marrow. After 2 wk of culture with the addition of several growth factors, the CD117(+) stem cells expanded approximately 20-fold and had an endothelial phenotype with high expression of CD34 and vascular endothelial-cadherin. However, >70% of these ex vivo expanded cells had a senescent phenotype by beta-galactosidase staining, and their survival and incorporation were poor after implantation into the ischemic limbs of mice. Compared with the PBS injection only, the microvessel density and the percentage of limb blood flow were significantly higher after the implantation of 2 x 10(5) freshly collected CD117(+) cells (P < 0.01) but not after the implantation of 2 x 10(5) expanded CD117(+) cells (P > 0.05). These data indicate that ex vivo expansion of CD117(+) stem cells has low potency for inducing therapeutic angiogenesis, which might be related to the cellular senescence during ex vivo expansion.
authors.affiliation: Department of Medical Bioregulation, Yamaguchi University School of Medicine, Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan.
authors.forename: Tao-Sheng
authors.initials: TS
authors.lastname: Li
authors.forename: Masanori
authors.initials: M
authors.lastname: Hayashi
authors.forename: Ze-Lin
authors.initials: ZL
authors.lastname: Liu
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ito
authors.forename: Akihito
authors.initials: A
authors.lastname: Mikamo
authors.forename: Akira
authors.initials: A
authors.lastname: Furutani
authors.forename: Masunori
authors.initials: M
authors.lastname: Matsuzaki
authors.forename: Kimikazu
authors.initials: K
authors.lastname: Hamano
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D002469:Cell Separation; D002470:Cell Survival; D002478:Cells, Cultured; D005434:Flow Cytometry; D018380:Hematopoietic Stem Cell Transplantation; D006614:Hindlimb / Q000098:blood supply / Q000502:physiology; D007511:Ischemia / Q000503:physiopathology / Q000628:therapy; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008833:Microcirculation / Q000502:physiology; D018919:Neovascularization, Physiologic / Q000502:physiology*; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D019009:Proto-Oncogene Proteins c-kit; D001616:beta-Galactosidase