Low angiogenic potency induced by the implantation of ex vivo expanded CD117(+) stem cells.
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.
Li
Tao-Sheng
TS
Department of Medical Bioregulation, Yamaguchi University School of Medicine, Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan.
Hayashi
Masanori
M
Liu
Ze-Lin
ZL
Ito
Hiroshi
H
Mikamo
Akihito
A
Furutani
Akira
A
Matsuzaki
Masunori
M
Hamano
Kimikazu
K
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
D019009:Proto-Oncogene Proteins c-kit; D001616:beta-Galactosidase