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适应性血液动力内皮细胞用于器官生成和瘤生成

Brisa Palikuqi¹, Duc-Huy T Nguyen¹, Ge Li¹

¹Division of Regenerative Medicine, Ansary Stem Cell Institute, Department of Medicine, Weill Cornell Medicine, New York, NY, USA.

|September 10, 2020

概括

在成熟的内皮细胞中,ETS变异转录因子2 (ETV2) 的过渡性重新激活会产生适应性的血管网络. 这些重置血管内皮细胞 (R-VEC) 能够进行器官血管化和组织修复.

科学领域:

血管生物学和再生医学
内皮细胞生物学和组织工程

背景情况:

成熟的内皮细胞在培养中丧失了组织特异性血管化的适应性.
器官的发育和再生依赖于特定组织的内皮细胞特征.

研究的目的:

确定ETS变异转录因子2 (ETV2) 的短暂重新激活是否可以恢复成熟的人体内皮细胞的适应性.
开发一种可扩展的器官血管化平台,并研究内皮细胞与细胞的相互作用.

主要方法:

培养成熟的人体内皮细胞在拉米尼-菌素类型IV原基质 (LEC) 中.
暂时重新激活ETV2以产生恢复的血管内皮细胞 (R-VEC).
评估微流体室中的R-VEC自我组装和小鼠体内植入.
使用R-VEC在一个新的"器官-血管网"平台与器官和瘤一起培养.
使用单细胞RNA测序和表观遗传特征分析R-VEC行为.

主要成果:

ETV2的重新激活将内皮细胞"重置"为血管生成的R-VEC,形成可 perfus 的血管.
在3D矩阵中,R-VEC自我组装成稳定的多层血管网络,并在体内与宿主循环进行解剖.
器官对血管网络使人类胰腺小岛,脱细胞化肠道和结肠器官的功能血管化成为可能.
R-VEC 建立了一个适应性血管,以特定组织的方式符合器官和瘤.

结论:

过时的ETV2重新激活使内皮细胞复原,使其能够进行器官型血管化.
器官对血管网络平台为研究器官对细胞交叉声提供了一个生理模型.
这种方法具有治疗器官修复和向癌症治疗的潜力.

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