A role for hematopoietic stem cells in promoting angiogenesis

A role for hematopoietic stem cells in promoting angiogenesis
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DOI:
10.1016/s0092-8674(00)00025-8
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发表时间:
2000-07-21
期刊:
影响因子:
64.5
通讯作者:
Suda, T
Suda, T
中科院分区:
生物学1区
文献类型:
--
作者:
Takakura, N;Watanabe, T;Suda, T

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血管生成是胚胎器官发生以及成人组织修复的重要事件。在这里,我们表明,造血干细胞(HSC)在胚胎发生过程中血管生成发挥重要作用。为了研究造血干细胞在内皮细胞(EC)发育中的作用,我们分析了AML 1缺陷的胚胎,这些胚胎缺乏明确的造血功能。这些胚胎在头部和心包中显示出缺陷的血管生成。Pars-aortic splanchnopalleum(P-Sp)外植体培养基质细胞(P-Sp培养)不产生永久性造血细胞,并显示有缺陷的血管生成在AML 1无效胚胎。通过加入HSC或血管生成素-1(Ang 1),从AML 1无效胚胎中获得的P-Sp培养物中的血管生成被破坏。表达Ang 1的HSC在体内和体外直接促进EC的迁移。这些结果表明,HSC是血管生成的关键。
Angiogenesis is an important event for embryonic organogenesis as well as for tissue repair in the adult. Here, we show that hematopoietic stem cells (HSCs) play important roles for angiogenesis during embryogenesis. To investigate the role of HSCs in endothelial cell (EC) development, we analyzed AML1-deficient embryos, which lack definitive hematopoiesis. These embryos showed defective angiogenesis in the head and pericardium. Pars-aortic splanchnopleural (P-Sp) explant cultures on stromal cells (P-Sp culture) did not generate definitive hematopoietic cells and showed defective angiogenesis in the AML1 null embryo. Disrupted angiogenesis in P-Sp cultures from AML1 null embryos was rescued by addition of HSCs or angiopoietin-1 (Ang1). HSCs, which express Ang1, directly promoted migration of ECs in vivo and in vitro. These results indicate that HSCs are critical for angiogenesis.