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Differentiation and expansion of endothelial cells requires pre-optimization of KDR+ expression kinetics.
Stem Cell Research ( IF 1.2 ) Pub Date : 2019-12-16 , DOI: 10.1016/j.scr.2019.101685
Basharat Jahan 1 , Kara E McCloskey 2
Affiliation  

Human endothelial cells (ECs) are important tools in research and development of new therapies in the fields of angiogenesis, vasculogenesis, engineering organoids and multicellular tissues, drug discovery, and disease modeling. Efficient and robust induction of ECs from human pluripotent stem cells (hPSCs) serve as a renewable and indefinite cell sources. However, individual lines of embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) are distinct and can often respond very differently to the same microenvironmental cues. Therefore, we set out to develop a differentiation methodology specifically designed for robustness across multiple human iPSC lines. In general, the key soluble signals remain consistent across cell lines, but because the differentiation and proliferation kinetics can differ slightly in hESC and iPSC cell lines, the time point for KDR+ cell sorting must be pre-determined for each cell line. This three-stage induction method uses three different chemically defined medium formulations and generates highly purified populations of actively proliferating and functional VE-cadherin+ ECs within 30 days.



中文翻译:

内皮细胞的分化和扩增需要KDR +表达动力学的预先优化。

人内皮细胞(EC)是在血管生成,血管生成,工程类器官和多细胞组织,药物发现和疾病建模等领域开发新疗法的重要工具。人类多能干细胞(hPSC)对EC的高效诱导可以作为可再生和不确定的细胞来源。但是,胚胎干细胞(hESC)和诱导性多能干细胞(iPSC)的各个系是截然不同的,并且通常对同一微环境线索的反应可能非常不同。因此,我们着手开发一种专为跨多个人iPSC系的稳健性而设计的差异化方法。通常,关键可溶性信号在细胞系之间保持一致,但由于hESC和iPSC细胞系的分化和增殖动力学可能略有不同,因此必须为每种细胞系预先确定KDR +细胞分选的时间点。这种三阶段诱导方法使用三种不同的化学成分确定的培养基配方,并在30天内生成高度纯化的活跃增殖和功能性VE-钙粘蛋白+ EC的群体。

更新日期:2019-12-16
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