The evaluation of drug pharmacokinetics in the small intestine is critical for developing orally administered drugs. Caucasian colon adenocarcinoma (Caco-2) cells are employed to evaluate drug absorption in preclinical trials of drug development. However, the pharmacokinetic characteristics of Caco-2 cells are different from those of the normal human small intestine. Besides this, it is almost impossible to obtain primary human intestinal epithelial cells of the same batch. Therefore, human iPS cell-derived enterocytes (hiPSEs) with pharmacokinetic functions similar to human intestinal epithelial cells are expected to be useful for the evaluation of drug absorption. Previous studies have been limited to the use of cytokines and small molecules to generate hiPSEs. Dietary fibers play a critical role in maintaining intestinal physiology. We used gellan gum (GG), a soluble dietary fiber, to optimize hiPSE differentiation. hiPSEs cocultured with GG had significantly higher expression of small intestine- and pharmacokinetics-related genes and proteins. The activities of drug-metabolizing enzymes, such as cytochrome P450 2C19, and peptide transporter 1 were significantly increased in the GG treatment group compared to the control group. At the end point of differentiation, the percentage of senescent cells increased. Therefore, GG could improve the differentiation efficiency of human iPS cells to enterocytes and increase intestinal maturation by extending the life span of hiPSEs.

中文翻译：

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结冷胶促进人类诱导的多能干细胞分化为肠上皮细胞。

小肠中药物药代动力学的评估对于开发口服药物至关重要。在药物开发的临床前试验中，白种人结肠腺癌（Caco-2）细胞用于评估药物吸收。但是，Caco-2细胞的药代动力学特征与正常人小肠的不同。除此之外，几乎不可能获得相同批次的原代人肠上皮细胞。因此，具有与人肠上皮细胞相似的药代动力学功能的人iPS细胞来源的肠上皮细胞（hiPSE）有望用于评估药物的吸收。先前的研究仅限于使用细胞因子和小分子产生hiPSE。膳食纤维在维持肠道生理中起着至关重要的作用。我们使用了吉兰糖胶（GG）（一种可溶性膳食纤维）来优化hiPSE分化。与GG共培养的hiPSE具有明显更高的小肠和药代动力学相关基因和蛋白质的表达。与对照组相比，GG治疗组的药物代谢酶（例如细胞色素P450 2C19和肽转运蛋白1）的活性显着增加。在分化的终点，衰老细胞的百分比增加。因此，GG可以通过延长hiPSE的寿命来提高人iPS细胞向肠细胞的分化效率并增加肠道成熟度。与对照组相比，GG治疗组的药物代谢酶（例如细胞色素P450 2C19和肽转运蛋白1）的活性显着增加。在分化的终点，衰老细胞的百分比增加。因此，GG可以通过延长hiPSE的寿命来提高人iPS细胞向肠细胞的分化效率并增加肠道成熟度。与对照组相比，GG治疗组的药物代谢酶（例如细胞色素P450 2C19和肽转运蛋白1）的活性显着增加。在分化的终点，衰老细胞的百分比增加。因此，GG可以通过延长hiPSE的寿命来提高人iPS细胞向肠细胞的分化效率并增加肠道成熟度。