Vasoprotective effects of human CD34+ cells: towards clinical applications.

Vasoprotective effects of human CD34+ cells: towards clinical applications.
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DOI:
10.1186/1479-5876-7-66
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发表时间:
2009-07-29
影响因子:
7.4
通讯作者:
Simari RD
Simari RD
中科院分区:
医学2区
文献类型:
--
作者:
Kiernan TJ;Boilson BA;Witt TA;Dietz AB;Lerman A;Simari RD

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人类细胞疗法的开发需要在动物模型中进行临床前测试。自体动物产品的使用未能解决来自人类的类似产品的有效性。我们使用了一种新的免疫缺陷大鼠颈动脉损伤模型,以确定人类细胞是否可以改善急性损伤后的血管重塑。使用自动磁性细胞分离从外周血沉棕黄层分离人CD 34+细胞。使用2F Fogarty球囊导管在雄性Sprague-Dawley裸大鼠中进行颈动脉损伤。通过腔内滴注局部施用新鲜收获的CD 34+细胞或单独的盐水20分钟。28天后进行动脉的结构和功能分析。形态学分析表明,与生理盐水相比,人CD 34+细胞递送与球囊损伤后4周内膜形成的显著减少相关(CD 34和生理盐水处理的血管的I/M比分别为0.79 ± 0.18和1.71 ± 0.18,P < 0.05)。血管反应性研究显示,与盐水处理的对应物相比,来自人CD 34+处理的动物的血管环的最大松弛显著增强(CD 34+细胞和盐水分别为74.1 ± 10.2和36.8 ± 12.1%松弛,P < 0.05)。人CD 34+细胞的递送限制新生内膜形成并改善血管损伤后的动脉反应性。这些研究推进了细胞递送的概念,以影响血管重塑,使其成为潜在的人类细胞产物。
The development of cell-based therapeutics for humans requires preclinical testing in animal models. The use of autologous animal products fails to address the efficacy of similar products derived from humans. We used a novel immunodeficient rat carotid injury model in order to determine whether human cells could improve vascular remodelling following acute injury. Human CD34+ cells were separated from peripheral buffy coats using automatic magnetic cell separation. Carotid arterial injury was performed in male Sprague-Dawley nude rats using a 2F Fogarty balloon catheter. Freshly harvested CD34+ cells or saline alone was administered locally for 20 minutes by endoluminal instillation. Structural and functional analysis of the arteries was performed 28 days later. Morphometric analysis demonstrated that human CD34+ cell delivery was associated with a significant reduction in intimal formation 4 weeks following balloon injury as compared with saline (I/M ratio 0.79 ± 0.18, and 1.71 ± 0.18 for CD34, and saline-treated vessels, respectively P < 0.05). Vasoreactivity studies showed that maximal relaxation of vessel rings from human CD34+ treated animals was significantly enhanced compared with saline-treated counterparts (74.1 ± 10.2, and 36.8 ± 12.1% relaxation for CD34+ cells and saline, respectively, P < 0.05) Delivery of human CD34+ cells limits neointima formation and improves arterial reactivity after vascular injury. These studies advance the concept of cell delivery to effect vascular remodeling toward a potential human cellular product.
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