Department of Anatomy and Embryology, Leiden University Medical Center, Einthovenweg 20, 2333ZC Leiden, the Netherlands.
Central Laboratory Animal Facility, Einthovenweg 20, 2333ZC Leiden, the Netherlands.
Stem Cell Reports. 2018 May 8;10(5):1642-1656. doi: 10.1016/j.stemcr.2018.03.012. Epub 2018 Apr 12.
Several studies have reported endothelial cell (EC) derivation from human induced pluripotent stem cells (hiPSCs). However, few have explored their functional properties in depth with respect to line-to-line and batch-to-batch variability and how they relate to primary ECs. We therefore carried out accurate characterization of hiPSC-derived ECs (hiPSC-ECs) from multiple (non-integrating) hiPSC lines and compared them with primary ECs in various functional assays, which included barrier function using real-time impedance spectroscopy with an integrated assay of electric wound healing, endothelia-leukocyte interaction under physiological flow to mimic inflammation and angiogenic responses in in vitro and in vivo assays. Overall, we found many similarities but also some important differences between hiPSC-derived and primary ECs. Assessment of vasculogenic responses in vivo showed little difference between primary ECs and hiPSC-ECs with regard to functional blood vessel formation, which may be important in future regenerative medicine applications requiring vascularization.
已有多项研究报道称，内皮细胞（endothelial cell，EC）可由诱导多能干细胞（induced pluripotent stem cells，hiPSCs）分化而来。然而，目前鲜有研究深入探讨 hiPSC-EC 细胞在不同批次间的功能特性及其与原代 EC 细胞的相关性，针对这一问题，我们对来源于多个（非整合型）hiPSC 系的 hiPSC-EC 细胞进行了精确的特征描述，并在多种功能测定中对其与原代 EC 细胞进行了比较，这些功能测定包括利用实时阻抗谱技术进行屏障功能测定，利用集成的电伤口愈合测定法进行生理流动条件下内皮细胞与白细胞的相互作用测定，以及在体外和体内测定中进行血管生成反应测定。总的来说，我们发现 hiPSC 衍生的 EC 细胞与原代 EC 细胞之间存在许多相似之处，但也存在一些重要差异。体内血管生成反应评估结果显示，原代 EC 细胞与 hiPSC-EC 细胞在功能性血管生成方面差异较小，这对于未来需要血管生成的再生医学应用可能非常重要。
