Microfluidic Chip-Based Modeling of Three-Dimensional Intestine-Vessel-Liver Interactions in Fluorotelomer Alcohol Biotransformation

被引：6

作者：

Xu, Ning ^{[1
]}

Lin, Haifeng ^{[2
]}

Lin, Jin-Ming ^{[3
]}

Cheng, Jie ^{[1
]}

Wang, Peilong ^{[1
]}

Lin, Ling ^{[2
]}

机构：

[1] Chinese Acad Agr Sci, Inst Qual Stand & Testing Technol Agroprod, Beijing 100081, Peoples R China

[2] Beijing Technol & Business Univ, Dept Bioengn, Beijing 100048, Peoples R China

[3] Tsinghua Univ, Dept Chem, MOE Key Lab Bioorgan Phosphorus Chem &Chem Biol, Beijing 100084, Peoples R China

来源：

ANALYTICAL CHEMISTRY | 2023年 / 95卷 / 46期

基金：

中国国家自然科学基金; 国家重点研发计划;

关键词：

CULTURE; METABOLISM; CELLS;

D O I：

10.1021/acs.analchem.3c03892

中图分类号：

O65 [分析化学];

学科分类号：

070302 ; 081704 ;

摘要：

Plyfluoroalkyl substance (PFAS), featured with incredible persistence and chronic toxicity, poses an emerging ecological and environmental crisis. Although significant progress has been made in PFAS metabolism in vivo, the underlying mechanism of metabolically active organ interactions in PFAS bioaccumulation remains largely unknown. We developed a microfluidic-based assay to recreate the intestine-vessel-liver interface in three dimensions, allowing for high-resolution, real-time images and precise quantification of intestine-vessel-liver interactions in PFAS biotransformation. In contrast to the scattered arrangement of vascular endothelium on the traditional d-polylysine-modified two-dimensional (2D) plate, the microtubules in our three-dimensional (3D) platform formed a dense honeycomb network through the ECM, with longer tubular structures. Additionally, the slope culture of epithelial cells in our platform exhibited a closely arranged and thicker cell layer than the planar culture. To dynamically monitor the metabolic crosstalk in the intestinal-vascular endothelium-liver interaction under exposure to fluorotelomer alcohols (FTOHs), we combined the chip with a solid-phase extraction-mass spectrometry (SPE-MS) system. Our findings revealed that endothelial cells were involved in the metabolic process of FTOHs. The transformation of intestinal epithelial and hepatic epithelial cells produces toxic metabolite fluorotelomer carboxylic acids (FTCAs), which circulate to endothelial cells and affect angiogenesis. This system shows promise as an enhanced surrogate model and platform for studying pollutant exposure as well as for biomedical and pharmaceutical research.

引用

页码：17064 / 17072

页数：9