Age-related BM-MNC dysfunction hampers neovascularization
Age-related BM-MNC dysfunction hampers neovascularization
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DOI：
10.1016/j.mad.2007.06.009
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发表时间：
2007-09-01
影响因子：
5.3
通讯作者：
Hisatome, Ichiro
中科院分区：
文献类型：
--
作者：
Sugihara, Shinobu;Yamamoto, Yasutaka;Hisatome, Ichiro
虽然缺血诱导的新血管形成据报道随着年龄的增长而受损，但老年骨髓单个核细胞（BMNINCs）对新血管形成的影响尚未研究。将从8周龄小鼠（年轻）获得的BM-MNC的新血管形成能力与从18月龄小鼠（年老）获得的BM-MNC的新血管形成能力进行体内和体外比较。老年小鼠缺血肢体的新生血管明显受损。而年轻的BM-MNC移植显着改善血液灌注，组织毛细血管密度，血管内皮生长因子（VEGF）的生产在移植缺血肢体，没有这样的效果与旧的BM-MNC观察。老年BM-MNCs也表现出显着的损伤，在体外VEGF的生产和迁移能力的VEGF。老年小鼠骨髓单个核细胞中Diulectin阳性细胞数明显减少，而AC 133（+）/CD 34（+）和CD 34（+）/VEGF-R2（+）阳性细胞数在青年和老年骨髓单个核细胞中无差异。年轻BM-MNCs的移植改善了老年受者缺血肢体的新血管形成和VEGF的产生，结果与年轻受者中获得的结果相似。这些结果表明，移植的BM-MNCs的新血管形成能力随着年龄的增长而受损。然而，老化并不妨碍新生血管的小鼠宿主中的年轻BM-MNCs移植的振兴。(C)2007爱思唯尔爱尔兰有限公司保留所有权利。
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. (C) 2007 Elsevier Ireland Ltd. All rights reserved.