Rapamycin suppresses self-renewal and vasculogenic potential of stem cells isolated from infantile hemangioma.
Rapamycin suppresses self-renewal and vasculogenic potential of stem cells isolated from infantile hemangioma.
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DOI：
10.1038/jid.2011.300
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发表时间：
2011-12
影响因子：
6.5
通讯作者：
Bischoff, Joyce
中科院分区：
文献类型：
--
作者：
Greenberger, Shoshana;Yuan, Siming;Walsh, Logan A.;Boscolo, Elisa;Kang, Kyu-Tae;Matthews, Benjamin;Mulliken, John B.;Bischoff, Joyce
婴儿血管瘤是一种常见的儿童血管性肿瘤。虽然是良性的，但有些血管瘤会导致特征的变形和破坏或危及生命。目前的治疗，皮质类固醇或普萘洛尔，是管理几个月，并可能有不利影响的婴儿。我们设计了一个高通量筛选来鉴定FDA批准的可用于治疗这种肿瘤的药物。雷帕霉素是一种mTOR抑制剂，基于其抑制血管瘤源性干细胞群增殖的能力而被鉴定，血管瘤源性干细胞群是我们先前发现的人血管生成细胞。体外和体内研究表明，雷帕霉素降低了血管瘤干细胞的自我更新能力，降低了分化潜力，并抑制了这些细胞在体内的血管生成活性。通过血管瘤干细胞形成的血管的血流的纵向体内成像显示，雷帕霉素也导致血管瘤血管的消退，与其已知的抗血管生成活性一致。最后，我们证明了雷帕霉素诱导的干性丧失可以与皮质类固醇（目前治疗有问题的血管瘤的标准疗法）协同工作，以阻止体内血管瘤的形成。我们的研究表明，雷帕霉素靶向患者来源的血管瘤干细胞的自我更新和血管分化潜力，并提出了一种新的治疗策略，以防止这种毁容和危及儿童肿瘤的形成。
Infantile hemangioma (IH) is a common childhood vascular tumor. Although benign, some hemangiomas cause deformation and destruction of features or endanger life. The current treatments, corticosteroid or propranolol, are administered for several months and can have adverse effects for the infant. We designed a high-throughput screen to identify FDA-approved drugs that could be used to treat this tumor. Rapamycin, an mTOR inhibitor, was identified based on its ability to inhibit proliferation of a hemangioma-derived stem cell population, human vasculogenic cells we had previously discovered. In vitro and in vivo studies show that Rapamycin reduces the self-renewal capacity of the hemangioma stem cells, diminishes differentiation potential, and inhibits the vasculogenic activity of these cells in vivo. Longitudinal in vivo imaging of blood flow through vessels formed with hemangioma stem cells shows that Rapamycin also leads to regression of hemangioma blood vessels, consistent with its known anti-angiogenic activity. Finally, we demonstrate that Rapamycin-induced loss of stemness can work in concert with corticosteroid, the current standard therapy for problematic hemangioma, to block hemangioma formation in vivo. Our studies reveal that Rapamycin targets the self-renewal and vascular differentiation potential in patient-derived hemangioma stem cells and suggests a novel therapeutic strategy to prevent formation of this disfiguring and endangering childhood tumor.
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DOI：
10.1111/j.1432-1033.1997.t01-2-00527.x
发表时间：
1997-01-15
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
Meijer, L;Borgne, A;Moulinoux, JP
通讯作者：
Moulinoux, JP
DOI：
10.1056/nejmoa0903036
发表时间：
2010-03-18
期刊：
The New England journal of medicine
影响因子：
--
作者：
Greenberger S;Boscolo E;Adini I;Mulliken JB;Bischoff J
通讯作者：
Bischoff J
DOI：
10.1084/jem.20081297
发表时间：
2008-09-29
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Chen C;Liu Y;Liu R;Ikenoue T;Guan KL;Liu Y;Zheng P
通讯作者：
Zheng P
影响因子：
1.5
作者：
Amir, J;Metzker, A;Reisner, S H
通讯作者：
Reisner, S H
影响因子：
15.9
作者：
Khan, Zia A.;Boscolo, Elisa;Bischoff, Joyce
通讯作者：
Bischoff, Joyce