Age-related BM-MNC dysfunction hampers neovascularization

作者：Sugihara Shinobu; Yamamoto Yasutaka^*; Matsuura Takashi; Narazaki Genta; Yamasaki Akira; Igawa Go; Matsubara Koichi; Miake Junichiro; Igawa Osamu; Shigemasa Chiaki; Hisatome Ichiro

来源：Mechanisms of Ageing and Development, 2007, 128(9): 511-516.

DOI：10.1016/j.mad.2007.06.009

• aging
• ischemia
• neovascularization
• bone marrow mononuclear cells
• VEGF

Although ischemia-induced neovascularization is reportedly impaired with aging, the effect of aged-bone marrow mononuclear cells (BMNINCs) on neovascularization has not been investigated. The neovascularization capacity of BM-MNCs obtained from 8-week-old mice (young) was compared to those obtained from 18-month-old mice (old), both in vivo and in vitro. Neovascularization in ischemic limbs was significantly impaired in old mice. Whereas transplantation of young BM-MNC significantly improved blood perfusion, tissue capillary density, and vascular endothelial growth factor (VEGF) production in transplanted ischemic limbs, no such effects were observed with old BM-MNCs. Old BM-MNCs also showed a significant impairment of in vitro VEGF production and migratory capacity in response to VEGF. The number of Diulectin-positive cells was significantly lower in old mice, but there was no difference in the number of AC133(+)/CD34(+) and CD34(+)/VEGF-R2(+) positive cells between young and old BM-MNCs. Transplantation of young BM-MNCs improved neovascularization and VEGF production in the ischernic limbs of old recipients, with results that were similar to those obtained in young recipients. These results indicate that the neovascularization capacity of transplanted BM-MNCs is impaired with aging. However, aging does not hamper the revitalization of neovascularization in the murine host in response to transplantation of young BM-MNCs.

• 出版日期2007-9