Transplantation of low dose CD34+Kdr+ cells promotes vascular and muscular regeneration in ischemic limbs
Transplantation of low dose CD34+Kdr+ cells promotes vascular and muscular regeneration in ischemic limbs
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DOI：
10.1096/fj.04-2192fje
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发表时间：
2004-09-01
期刊：
影响因子：
4.8
通讯作者：
Peschle, C
中科院分区：
文献类型：
--
作者：
Madeddu, P;Emanueli, C;Peschle, C
造血祖细胞移植可促进缺血组织的血管重建。然而，有待移植的最佳细胞群尚未确定。我们比较了表达VEGF-A受体2（KDR）或不表达的两种人脐带血CD 34（+）祖细胞亚群的治疗潜力。在无血清饥饿培养中，与CD 34（+）KDR（-）细胞相比，CD 34（+）KDR（+）细胞显示出更强的抗凋亡和释放VEGF-A的能力。当注射到单侧缺血的免疫缺陷SCIDbg小鼠的后肢肌肉中时，低剂量（103）的CD 34（+）KDR（+）细胞比大剂量（10（4））的CD 34（+）KDR-细胞更好地改善了肢体挽救和血流动力学恢复。KDR+细胞诱导的新生血管形成明显上级KDR-细胞。同样，内皮细胞凋亡和间质纤维化显着减弱KDR+细胞，分化成成熟的人内皮细胞，也显然是骨骼肌细胞。这项研究表明，少量的CD 34（+）KDR（+）细胞有利于肢体缺血的修复性新血管形成和可能的肌生成，这表明该细胞群在再生医学中的潜在用途。
Hematopoietic progenitor cell transplantation can contribute to revascularization of ischemic tissues. Yet, the optimal cell population to be transplanted has yet to be determined. We have compared the therapeutic potential of two subsets of human cord blood CD34(+) progenitors, either expressing the VEGF-A receptor 2 (KDR) or not. In serum-free starvation culture, CD34(+)KDR(+) cells reportedly showed greater resistance to apoptosis and ability to release VEGF-A, as compared with CD34(+)KDR(-) cells. When injected into the hind muscles in immunodeficient SCIDbg mice subjected to unilateral ischemia, a low number ( 103) of CD34(+)KDR(+) cells improved limb salvage and hemodynamic recovery better than a larger dosage (10(4)) of CD34(+) KDR- cells. The neovascularization induced by KDR+ cells was significantly superior to that promoted by KDR- cells. Similarly, endothelial cell apoptosis and interstitial fibrosis were significantly attenuated by KDR+ cells, which differentiated into mature human endothelial cells and also apparently skeletal muscle cells. This study demonstrates that a low number of CD34(+)KDR(+) cells favors reparative neovascularization and possibly myogenesis in limb ischemia, suggesting the potential use of this cell population in regenerative medicine.