Identification of functional endothelial progenitor cells suitable for the treatment of ischemic tissue using human umbilical cord blood
Identification of functional endothelial progenitor cells suitable for the treatment of ischemic tissue using human umbilical cord blood
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DOI：
10.1182/blood-2006-10-047092
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发表时间：
2007-07-01
期刊：
影响因子：
20.3
通讯作者：
Ohneda, Osamu
中科院分区：
文献类型：
--
作者：
Nagano, Masumi;Yamashita, Toshiharu;Ohneda, Osamu
脐带血（UCB）已被用作各种干细胞的潜在来源，包括造血干细胞、间充质干细胞和内皮祖细胞（EPCs），用于各种细胞治疗。近年来，内皮祖细胞被用于缺血组织血管化的修复。从脐带血中分离内皮祖细胞是提高治疗效果和消除非必需细胞意外扩增的关键问题。在这里，我们报告了一种新的方法，分离内皮祖细胞从脐带血相结合的负性免疫选择和细胞培养技术。此外，我们根据乙醛脱氢酶（ALDH）活性将EPCs分为两个亚群。我们发现具有低ALDH活性的EPCs（Alde-Low）比具有高ALDH活性的EPCs（Alde-High）具有更大的增殖和迁移能力。此外，低氧诱导因子蛋白在低氧条件下在Alde低EPCs中上调，VEGF、CXCR 4和GLUT-1 mRNA在低氧条件下增加，而在Alde高EPCs中反应不显著。事实上，在小鼠皮瓣模型中，Alde-Low EPCs的引入显著减少了缺血中的组织损伤。因此，导入Alde-Low EPCs可能是诱导缺血组织快速新生血管和随后再生的潜在策略。
Umbilical cord blood (UCB) has been used as a potential source of various kinds of stem cells, including hematopoietic stem cells, mesenchymal stem cells, and endothelial progenitor cells (EPCs), for a variety of cell therapies. Recently, EPCs were introduced for restoring vascularization in ischemic tissues. An appropriate procedure for isolating EPCs from UCB is a key issue for improving therapeutic efficacy and eliminating the unexpected expansion of nonessential cells. Here we report a novel method for isolating EPCs from UCB by a combination of negative immunoselection and cell culture techniques. In addition, we divided EPCs into 2 subpopulations according to the aldehyde dehydrogenase (ALDH) activity. We found that EPCs with low ALDH activity (Alde-Low) possess a greater ability to proliferate and migrate compared to those with high ALDH activity (Alde-High). Moreover, hypoxia-inducible factor proteins are up-regulated and VEGF, CXCR4, and GLUT-1 mRNAs are increased in Alde-Low EPCs under hypoxic conditions, while the response was not significant in Alde-High EPCs. In fact, the introduction of Alde-Low EPCs significantly reduced tissue damage in ischemia in a mouse flap model. Thus, the introduction of Alde-Low EPCs may be a potential strategy for inducing rapid neovascularization and subsequent regeneration of ischemic tissues.