Rapamycin inhibits proliferation and differentiation of human endothelial progenitor cells in vitro
Rapamycin inhibits proliferation and differentiation of human endothelial progenitor cells in vitro
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DOI：
10.1016/j.yexcr.2004.07.002
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发表时间：
2004-10-15
影响因子：
3.7
通讯作者：
Fiedler, W
中科院分区：
文献类型：
--
作者：
Butzal, M;Loges, S;Fiedler, W
骨髓来源的循环内皮前体细胞有助于各种疾病中的新血管生成。雷帕霉素最近在实验性肿瘤模型中被证明具有抗血管生成作用。我们的小组已经开发了一种培养系统，允许人CD 133（+）前体细胞的扩增和内皮分化。我们可以通过PCR分析表明，雷帕霉素结合蛋白mTOR在新鲜的CD 133+细胞、28天后扩增的细胞和分化的内皮细胞中表达。雷帕霉素在与造血Jurkat或HL-60细胞相似的浓度下剂量依赖性地抑制CD 133+细胞的增殖。雷帕霉素诱导细胞凋亡后48它的治疗，这可以减少与FK 506预孵育。此外，从扩增的CD 133+细胞的粘附内皮细胞的发育受到剂量依赖性抑制。内皮抗原CD 144和血管性血友病因子在分化的内皮前体细胞上的表达被雷帕霉素降低。总之，雷帕霉素抑制人内皮前体细胞的增殖和分化，强调了其抗血管生成作用。(C)2004年爱思唯尔公司All rights reserved.
Bone-marrow-derived, circulating endothelial precursor cells contribute to neoangiogenesis in various diseases. Rapamycin has recently been shown to have anti-angiogenic effects in an experimental tumor model. Our group has developed a culture system that allows expansion and endothelial differentiation of human CD133(+) precursor cells. We could show by PCR analysis that mTOR, the rapamycin-binding protein, was expressed in fresh CD133+ cells, in expanded cells after 28 days, and in differentiated endothelial cells. Rapamycin inhibited proliferation of CD133+ cells dose dependently at similar concentrations as hematopoietic Jurkat or HL-60 cells. Apoptosis was induced by rapamycin after 48 It of treatment, which could be reduced by preincubation with FK 506. Furthermore, the development of adherent endothelial cells from expanded CD133+ cells was dose dependently inhibited. Expression of endothelial antigens CD144 and von Willebrand factor on differentiating endothelial precursors was reduced by rapamycin. In summary, rapamycin inhibits proliferation and differentiation of human endothelial precursor cells underlining its anti-angiogenic effects. (C) 2004 Elsevier Inc. All rights reserved.