Angiopoietin-like proteins stimulate ex vivo expansion of hematopoietic stem cells
Angiopoietin-like proteins stimulate ex vivo expansion of hematopoietic stem cells
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DOI：
10.1038/nm1342
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发表时间：
2006-02-01
期刊：
影响因子：
82.9
通讯作者：
Lodish, HF
中科院分区：
文献类型：
--
作者：
Zhang, CC;Kaba, M;Lodish, HF
造血干细胞的成功体外扩增将极大地有利于疾病的治疗和对干细胞生物学关键问题的理解。在这里，我们显示，使用微阵列研究，HSC支持的小鼠胎肝CD3（+）细胞特异性表达血管生成素样蛋白2（Angptl2）和血管生成素样蛋白3（Angptl3）。当我们在Angptl2或Angptl3以及饱和水平的其它生长因子存在下培养高度富集的HSC 10天时，我们通过重建分析观察到长期HSC的24或30倍净扩增。Angptl2的卷曲螺旋结构域能够刺激HSC的扩增。此外，血管生成素样5、血管生成素样7和微纤维相关糖蛋白4也支持培养中HSC的扩增。
Successful ex vivo expansion of hematopoietic stem cells (HSCs) would greatly benefit the treatment of disease and the understanding of crucial questions of stem cell biology. Here we show, using microarray studies, that the HSC-supportive mouse fetal liver CD3(+) cells specifically express the proteins angiopoietin-like 2 (Angptl2) and angiopoietin-like 3 (Angptl3). We observed a 24- or 30-fold net expansion of long- term HSCs by reconstitution analysis when we cultured highly enriched HSCs for 10 days in the presence of Angptl2 or Angptl3 together with saturating levels of other growth factors. The coiled-coil domain of Angptl2 was capable of stimulating expansion of HSCs. Furthermore, angiopoietin-like 5, angiopoietin-like 7 and microfibril-associated glycoprotein 4 also supported expansion of HSCs in culture.