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A simple three-dimensional gut model constructed in a restricted ductal microspace induces intestinal epithelial cell integrity and facilitates absorption assays.
Biomaterials Science ( IF 5.8 ) Pub Date : 2020-08-31 , DOI: 10.1039/d0bm00763c Tadaaki Nakajima 1 , Katsunori Sasaki , Akihiro Yamamori , Kengo Sakurai , Kaori Miyata , Tomoyuki Watanabe , Yukiko T Matsunaga
Biomaterials Science ( IF 5.8 ) Pub Date : 2020-08-31 , DOI: 10.1039/d0bm00763c Tadaaki Nakajima 1 , Katsunori Sasaki , Akihiro Yamamori , Kengo Sakurai , Kaori Miyata , Tomoyuki Watanabe , Yukiko T Matsunaga
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The intestine acts as a center for nutrient and water absorption at the epithelium and plays an important role in immunity. Considering the complexity of its function and roles in living systems, a physiologically relevant gut in vitro model is desirable in both basic biology and the analysis of effects of some substances on functions of the gut; these analyses include the screening of drug and food candidates with regard to intestinal disorder at an early stage of medical development. In the present study, we constructed a three-dimensional (3D) gut model using human absorptive enterocytes (CACO-2 cells) by reconstitution of the gut epithelial sheet restricted on a high-reproducible ductal scaffold of collagen gel. Moreover, using the 3D gut model, we evaluated the morphology at the cellular and tissue levels and conducted a phenotypic analysis of the intestinal physiological functions, which involved a permeability assay mimicking barrier disruption inducing inflammation and an absorption assay reflecting ingestive effects. The ductal structure, in vivo-like 3D epithelial structures, epithelial barrier, and effective absorptive function characterized the 3D gut model. The epithelial cells formed a villus-like buckling epithelium, vertical microvilli of increased density on the cell surface, and a crypt-like localized cell proliferating region. The mature shape of the epithelium may contribute to mimicking barrier function and effective absorption compared with that in the 2D gut model. Furthermore, we successfully mimicked the dextran sodium sulfate-induced epithelial barrier dysfunction as a trigger phenomenon of gut inflammation in the 3D gut model. The integrity of the epithelium and phenotypic analysis of the intestinal physiological functions in the simple and reproducible 3D gut model will allow for a drug screening system for assessing the effects on the functions of the gut epithelium from the lumen side.
中文翻译：
在受限的导管微空间中构建的简单三维肠模型可诱导肠上皮细胞完整性并促进吸收测定。
肠是上皮中营养和水分吸收的中心，在免疫中起重要作用。考虑到其功能和在生命系统中的作用的复杂性，在体外具有生理相关性在基础生物学和某些物质对肠道功能的影响分析中，模型是理想的；这些分析包括在医学发展的早期阶段筛查有关肠道疾病的药物和食物候选物。在本研究中，我们通过限制在胶原凝胶的高重复性导管支架上的肠道上皮层的重建，使用人类吸收性肠上皮细胞（CACO-2细胞）构建了三维（3D）肠道模型。此外，使用3D肠道模型，我们评估了细胞和组织水平的形态，并对肠道生理功能进行了表型分析，其中包括模拟诱导屏障炎症的屏障破坏的通透性测定和反映食入作用的吸收测定。导管结构体内类3D上皮结构，上皮屏障和有效吸收功能是3D肠模型的特征。上皮细胞形成绒毛状屈曲上皮，细胞表面密度增加的垂直微绒毛和隐窝状局部细胞增殖区。与2D肠模型相比，上皮的成熟形状可能有助于模仿屏障功能和有效吸收。此外，我们成功地模拟了葡聚糖硫酸钠诱导的上皮屏障功能障碍，将其作为3D肠道模型中肠道炎症的触发现象。
更新日期：2020-10-13
中文翻译：
在受限的导管微空间中构建的简单三维肠模型可诱导肠上皮细胞完整性并促进吸收测定。
肠是上皮中营养和水分吸收的中心，在免疫中起重要作用。考虑到其功能和在生命系统中的作用的复杂性，在体外具有生理相关性在基础生物学和某些物质对肠道功能的影响分析中，模型是理想的；这些分析包括在医学发展的早期阶段筛查有关肠道疾病的药物和食物候选物。在本研究中，我们通过限制在胶原凝胶的高重复性导管支架上的肠道上皮层的重建，使用人类吸收性肠上皮细胞（CACO-2细胞）构建了三维（3D）肠道模型。此外，使用3D肠道模型，我们评估了细胞和组织水平的形态，并对肠道生理功能进行了表型分析，其中包括模拟诱导屏障炎症的屏障破坏的通透性测定和反映食入作用的吸收测定。导管结构体内类3D上皮结构，上皮屏障和有效吸收功能是3D肠模型的特征。上皮细胞形成绒毛状屈曲上皮，细胞表面密度增加的垂直微绒毛和隐窝状局部细胞增殖区。与2D肠模型相比，上皮的成熟形状可能有助于模仿屏障功能和有效吸收。此外，我们成功地模拟了葡聚糖硫酸钠诱导的上皮屏障功能障碍，将其作为3D肠道模型中肠道炎症的触发现象。
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