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迈向全层小肠模型:基质细胞的掺入。

Towards Full Thickness Small Intestinal Models: Incorporation of Stromal Cells.

机构信息

Department of Molecular Cell Biology and Immunology, Amsterdam UMC, Vrije Universiteit, Amsterdam, The Netherlands.

Laboratory Medical Immunology, Amsterdam University Medical Center, Amsterdam, The Netherlands.

出版信息

Tissue Eng Regen Med. 2024 Apr;21(3):369-377. doi: 10.1007/s13770-023-00600-6. Epub 2023 Dec 19.

Abstract

INTRODUCTION

Since small intestine is one of the major barriers of the human body, there is a need to develop reliable in vitro human small intestinal models. These models should incorporate both the epithelial and lamina propria compartments and have similar barrier properties compared to that of the human tissue. These properties are essential for various applications, such as studying cell-cell interaction, intestinal diseases and testing permeability and metabolism of drugs and other compounds. The small intestinal lamina propria contains multiple stromal cell populations with several important functions, such as secretion of extracellular matrix proteins and soluble mediators. In addition, stromal cells influence the intestinal epithelial barrier, support the intestinal stem cell niche and interact with immune cells.

METHODS

In this review, we provide an extensive overview on the different types of lamina propria stromal cells found in small intestine and describe a combination of molecular markers that can be used to distinguish each different stromal cell type. We focus on studies that incorporated stromal cells into human representative small intestine models cultured on transwells.

RESULTS AND CONCLUSION

These models display enhanced epithelial morphology, increased cell proliferation and human-like barrier properties, such as low transepithelial electrical resistance (TEER) and intermediate permeability, thus better mimicking the native human small intestine than models only consisting of an epithelium which generally show high TEER and low permeability.

摘要

简介

由于小肠是人体的主要屏障之一,因此需要开发可靠的体外人小肠模型。这些模型应同时包含上皮和固有层隔室,并具有与人体组织相似的屏障特性。这些特性对于各种应用非常重要,例如研究细胞-细胞相互作用、肠道疾病以及测试药物和其他化合物的通透性和代谢。小肠固有层包含多种具有多种重要功能的基质细胞群体,例如细胞外基质蛋白和可溶性介质的分泌。此外,基质细胞还影响肠道上皮屏障,支持肠道干细胞龛,并与免疫细胞相互作用。

方法

在这篇综述中,我们广泛概述了在小肠中发现的不同类型的固有层基质细胞,并描述了可用于区分每种不同基质细胞类型的组合分子标记。我们重点介绍了将基质细胞整合到在 Transwell 上培养的人代表性小肠模型中的研究。

结果和结论

这些模型显示出增强的上皮形态、增加的细胞增殖和类似人类的屏障特性,例如低跨上皮电阻 (TEER) 和中等通透性,因此比仅由上皮组成的模型更好地模拟天然人小肠,上皮组成的模型通常具有高 TEER 和低通透性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/608a/10987430/dd8346b9955c/13770_2023_600_Fig1_HTML.jpg

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