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Low angiogenic potency induced by the implantation of ex vivo expanded CD117⁺ stem cells

Department of Medical Bioregulation, Division of Cardiovascular Surgery and Medicine, Yamaguchi University School of Medicine, Yamaguchi 755-8505, Japan

Submitted 9 October 2003 ; accepted in final form 24 November 2003

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 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 -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 10⁵ freshly collected CD117⁺ cells (P < 0.01) but not after the implantation of 2 x 10⁵ 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.

ischemic; blood flow; senescence; differentiation

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