Isolation and angiogenesis by endothelial progenitors in the fetal liver

Isolation and angiogenesis by endothelial progenitors in the fetal liver
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DOI:
10.1634/stemcells.2005-0070
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发表时间:
2006-01-01
期刊:
影响因子:
5.2
通讯作者:
Salomon, DR
Salomon, DR
中科院分区:
医学2区
文献类型:
--
作者:
Cherqui, S;Kurian, SM;Salomon, DR

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内皮祖细胞(EPC)具有显著的治疗潜力。然而,从骨髓中获得的此类细胞数量很少,而且它们在培养中增殖的能力有限,这使得它们的使用变得困难。在这里,我们提出了第一个确凿的证据,证明在小鼠胎肝中存在真正的内皮祖细胞,能够在移植后在体内形成连接到宿主血管系统的血管。这一群体特别令人感兴趣,因为它可以以高产量获得,并且与骨髓来源的内皮祖细胞相比具有高的血管生成能力。EPC容量包含在CD31(+)Sca1(+)细胞子集内。我们证明,这些细胞的生存和增殖依赖于来自胎肝的饲养层细胞单层。此外,我们还描述了一种新的、简单的方法来分离和体外增殖这些内皮祖细胞。最后,我们利用基因表达谱和串联质谱学蛋白质组学方法检测胎肝内皮祖细胞和饲养层细胞,以确定可能的促血管生成生长因子和内皮分化相关基因。
Endothelial progenitor cells (EPCs) have significant therapeutic potential. However, the low quantity of such cells available from bone marrow and their limited capacity to proliferate in culture make their use difficult. Here, we present the first definitive demonstration of the presence of true EPCs in murine fetal liver capable of forming blood vessels in vivo connected to the host's vasculature after transplantation. This population is particularly interesting because it can be obtained at high yield and has a high angiogenic capacity as compared with bone marrow-derived EPCs. The EPC capacity is contained within the CD31(+)Sca1(+) cell subset. We demonstrate that these cells are dependent for survival and proliferation on a feeder cell monolayer derived from the fetal liver. In addition, we describe a novel and easy method for the isolation and ex vivo proliferation of these EPCs. Finally, we used gene expression profiling and tandem mass spectrometry proteomics to examine the fetal liver endothelial progenitors and the feeder cells to identify possible proangiogenic growth factor and endothelial differentiation-associated genes.