人类可以通过多种接触途径（包括饮食）接触全氟烷基物质和多氟烷基物质 (PFAS)，这可能会导致多种不良健康影响。到目前为止，人们对 PFAS 穿过人体肠道屏障的转运知之甚少。在当前的研究中，我们旨在评估 5 种 PFAS（PFOS、PFOA、PFNA、PFHxS 和 HFPO-DA）在人诱导多能干细胞 (hiPSC) 衍生的肠上皮细胞 (IEC) 模型中的转运。该模型得到了广泛的表征，并与广泛应用的人结肠腺癌细胞系 Caco-2 和基于 IEC 的人原代模型进行了比较，被描述为最接近体内组织。 hiPSC 衍生的 IEC 层展示了具有紧密连接和粘液层的极化单层。单层细胞由肠上皮细胞、干细胞、杯状细胞、肠内分泌细胞和潘氏细胞组成，这些细胞也存在于天然组织中。转录组学分析揭示了基因表达谱的明显差异，其中与基于 IEC 的主要模型相比，hiPSC 衍生的 IEC 表现出肠道组织特异性基因的最高表达，而 Caco-2 细胞比基于 IEC 的主要模型更接近于聚集hiPSC 衍生的 IEC。模型之间 PFAS 传输的顺序在很大程度上相似，在 hiPSC 衍生的 IEC 模型中，从心尖到基底外侧方向 PFAS 的表观渗透性 (Papp) 值按以下顺序排列：PFHxS > PFOA > HFPO-DA > PFNA > PFOS 。总之，hiPSC 衍生的 IEC 模型与人类肠道生理学高度相似，因此是一种有前途的新型体外模型，可用于研究化学品穿过肠道屏障的运输以进行化学品风险评估。© 2024。作者。

Humans can be exposed to per- and polyfluoroalkyl substances (PFASs) via many exposure routes, including diet, which may lead to several adverse health effects. So far, little is known about PFAS transport across the human intestinal barrier. In the current study, we aimed to assess the transport of 5 PFASs (PFOS, PFOA, PFNA, PFHxS and HFPO-DA) in a human induced pluripotent stem cell (hiPSC)-derived intestinal epithelial cell (IEC) model. This model was extensively characterized and compared with the widely applied human colonic adenocarcinoma cell line Caco-2 and a human primary IEC-based model, described to most closely resemble in vivo tissue. The hiPSC-derived IEC layers demonstrated polarized monolayers with tight junctions and a mucus layer. The monolayers consisted of enterocytes, stem cells, goblet cells, enteroendocrine cells, and Paneth cells that are also present in native tissue. Transcriptomics analysis revealed distinct differences in gene expression profiles, where the hiPSC-derived IECs showed the highest expression of intestinal tissue-specific genes relative to the primary IEC-based model and the Caco-2 cells clustered closer to the primary IEC-based model than the hiPSC-derived IECs. The order of PFAS transport was largely similar between the models and the apparent permeability (Papp) values of PFAS in apical to basolateral direction in the hiPSC-derived IEC model were in the following order: PFHxS > PFOA > HFPO-DA > PFNA > PFOS. In conclusion, the hiPSC-derived IEC model highly resembles human intestinal physiology and is therefore a promising novel in vitro model to study transport of chemicals across the intestinal barrier for risk assessment of chemicals.© 2024. The Author(s).