全氟烷基物质在人诱导多能干细胞衍生的肠上皮细胞与原代人肠上皮细胞和 Caco-2 细胞之间的转运比较。

IF 4.8 2区 医学 Q1 TOXICOLOGY Archives of Toxicology Pub Date : 2024-08-31 DOI:10.1007/s00204-024-03851-x
Aafke W. F. Janssen, Loes P. M. Duivenvoorde, Karsten Beekmann, Nicole Pinckaers, Bart van der Hee, Annelies Noorlander, Liz L. Leenders, Jochem Louisse, Meike van der Zande
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引用次数: 0

摘要

人类可通过饮食等多种途径接触到全氟烷基和多氟烷基物质(PFAS),这可能会对健康造成多种不利影响。迄今为止,人们对 PFAS 通过人体肠道屏障的转运知之甚少。在本研究中,我们旨在评估 5 种 PFAS(PFOS、PFOA、PFNA、PFHxS 和 HFPO-DA)在人类诱导多能干细胞(hiPSC)衍生的肠上皮细胞(IEC)模型中的转运情况。该模型具有广泛的特征,并与广泛应用的人类结肠腺癌细胞系 Caco-2 和基于人类原代 IEC 的模型进行了比较,后者被描述为最接近体内组织。hiPSC 衍生的 IEC 层显示出具有紧密连接和粘液层的极化单层。单层包括肠细胞、干细胞、鹅口疮细胞、肠内分泌细胞和Paneth细胞,这些细胞也存在于原生组织中。转录组学分析揭示了基因表达谱的明显差异,与基于原生 IEC 的模型相比,源于 hiPSC 的 IEC 显示出最高的肠组织特异性基因表达量,而 Caco-2 细胞比源于 hiPSC 的 IEC 更接近于基于原生 IEC 的模型。两种模型的 PFAS 转运顺序基本相似,在 hiPSC 衍生 IEC 模型中,PFAS 的表观渗透性(Papp)值从顶端到基底侧的顺序如下:PFHxS > PFOA > HFPO-DA > PFNA > PFOS。总之,源于 hiPSC 的 IEC 模型与人类肠道生理结构高度相似,因此是研究化学品通过肠道屏障转运以进行化学品风险评估的一种很有前途的新型体外模型。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Transport of perfluoroalkyl substances across human induced pluripotent stem cell-derived intestinal epithelial cells in comparison with primary human intestinal epithelial cells and Caco-2 cells

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.

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来源期刊
Archives of Toxicology
Archives of Toxicology 医学-毒理学
CiteScore
11.60
自引率
4.90%
发文量
218
审稿时长
1.5 months
期刊介绍: Archives of Toxicology provides up-to-date information on the latest advances in toxicology. The journal places particular emphasis on studies relating to defined effects of chemicals and mechanisms of toxicity, including toxic activities at the molecular level, in humans and experimental animals. Coverage includes new insights into analysis and toxicokinetics and into forensic toxicology. Review articles of general interest to toxicologists are an additional important feature of the journal.
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