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
{"title":"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。","authors":"Aafke W. F. Janssen,&nbsp;Loes P. M. Duivenvoorde,&nbsp;Karsten Beekmann,&nbsp;Nicole Pinckaers,&nbsp;Bart van der Hee,&nbsp;Annelies Noorlander,&nbsp;Liz L. Leenders,&nbsp;Jochem Louisse,&nbsp;Meike van der Zande","doi":"10.1007/s00204-024-03851-x","DOIUrl":null,"url":null,"abstract":"<div><p>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 (<i>P</i><sub>app</sub>) values of PFAS in apical to basolateral direction in the hiPSC-derived IEC model were in the following order: PFHxS &gt; PFOA &gt; HFPO-DA &gt; PFNA &gt; 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.</p></div>","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":null,"pages":null},"PeriodicalIF":4.8000,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00204-024-03851-x.pdf","citationCount":"0","resultStr":"{\"title\":\"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\",\"authors\":\"Aafke W. F. Janssen,&nbsp;Loes P. M. Duivenvoorde,&nbsp;Karsten Beekmann,&nbsp;Nicole Pinckaers,&nbsp;Bart van der Hee,&nbsp;Annelies Noorlander,&nbsp;Liz L. Leenders,&nbsp;Jochem Louisse,&nbsp;Meike van der Zande\",\"doi\":\"10.1007/s00204-024-03851-x\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>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 (<i>P</i><sub>app</sub>) values of PFAS in apical to basolateral direction in the hiPSC-derived IEC model were in the following order: PFHxS &gt; PFOA &gt; HFPO-DA &gt; PFNA &gt; 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.</p></div>\",\"PeriodicalId\":8329,\"journal\":{\"name\":\"Archives of Toxicology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.8000,\"publicationDate\":\"2024-08-31\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://link.springer.com/content/pdf/10.1007/s00204-024-03851-x.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Archives of Toxicology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://link.springer.com/article/10.1007/s00204-024-03851-x\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"TOXICOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Archives of Toxicology","FirstCategoryId":"3","ListUrlMain":"https://link.springer.com/article/10.1007/s00204-024-03851-x","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"TOXICOLOGY","Score":null,"Total":0}
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。

摘要图片

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
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.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
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.
期刊最新文献
Establishment of a human 3D in vitro liver-bone model as a potential system for drug toxicity screening. The emerging role of alternatively activated macrophages to treat acute liver injury. Development and validation of an UPLC-ESI-MS/MS method for simultaneous quantification of antineoplastic agents and their metabolites in human plasma after unintentional exposure. Telmisartan potentiates the ITE-induced aryl hydrocarbon receptor activity in human liver cell line. Therapeutic potential of 4-phenylbutyric acid against methylmercury-induced neuronal cell death in mice.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1