Human induced pluripotent stem cells (hiPSCs) are used to study organogenesis and model disease as well as being developed for regenerative medicine. Endothelial cells are among the many cell types differentiated from hiPSCs, but their maturation and stabilization fall short of that in adult endothelium. We examined whether shear stress alone or in combination with pericyte co-culture would induce flow alignment and maturation of hiPSC-derived endothelial cells (hiPSC-ECs) but found no effects comparable with those in primary microvascular ECs. In addition, hiPSC-ECs lacked a luminal glycocalyx, critical for vasculature homeostasis, shear stress sensing, and signaling. We noted, however, that hiPSC-ECs have dysfunctional mitochondrial permeability transition pores, resulting in reduced mitochondrial function and increased reactive oxygen species. Closure of these pores by cyclosporine A improved EC mitochondrial function but also restored the glycocalyx such that alignment to flow took place. These results indicated that mitochondrial maturation is required for proper hiPSC-EC functionality.

人类诱导的多能干细胞（hiPSC）被用于研究器官发生和模型疾病，并被开发用于再生医学。内皮细胞是从hiPSC分化出的许多细胞类型中的一种，但它们的成熟和稳定能力不及成人内皮细胞。我们检查了剪切应力是否单独或与周细胞共培养相结合是否会引起hiPSC来源的内皮细胞（hiPSC-ECs）的流向排列和成熟，但没有发现与原代微血管EC相当的效果。此外，hiPSC-EC缺少腔糖萼，这对脉管系统的动态平衡，剪切应力感测和信号传导至关重要。但是，我们注意到，hiPSC-EC具有功能异常的线粒体通透性过渡孔，导致线粒体功能降低和活性氧增加。环孢菌素A封闭了这些孔，改善了EC线粒体功能，但同时也还原了糖萼，从而使流动顺畅。这些结果表明线粒体成熟是正确的hiPSC-EC功能所必需的。