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坏死性小肠结肠炎:体外模型概述。

Necrotizing Enterocolitis: Overview on In Vitro Models.

机构信息

Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy.

Pediatric Oncology and Hematology "Lalla Seragnoli", Pediatric Unit-IRCCS Azienda Ospedaliero-Universitaria, 40138 Bologna, Italy.

出版信息

Int J Mol Sci. 2021 Jun 23;22(13):6761. doi: 10.3390/ijms22136761.

Abstract

Necrotizing enterocolitis (NEC) is a gut inflammatory disorder which constitutes one of the leading causes of morbidity and mortality for preterm infants. The pathophysiology of NEC is yet to be fully understood; several observational studies have led to the identification of multiple factors involved in the pathophysiology of the disease, including gut immaturity and dysbiosis of the intestinal microbiome. Given the complex interactions between microbiota, enterocytes, and immune cells, and the limited access to fetal human tissues for experimental studies, animal models have long been essential to describe NEC mechanisms. However, at present there is no animal model perfectly mimicking human NEC; furthermore, the disease mechanisms appear too complex to be studied in single-cell cultures. Thus, researchers have developed new approaches in which intestinal epithelial cells are exposed to a combination of environmental and microbial factors which can potentially trigger NEC. In addition, organoids have gained increasing attention as promising models for studying NEC development. Currently, several in vitro models have been proposed and have contributed to describe the disease in deeper detail. In this paper, we will provide an updated review of available in vitro models of NEC and an overview of current knowledge regarding its molecular underpinnings.

摘要

坏死性小肠结肠炎(NEC)是一种肠道炎症性疾病,是早产儿发病和死亡的主要原因之一。NEC 的发病机制尚未完全阐明;多项观察性研究已经确定了多种与疾病发病机制相关的因素,包括肠道不成熟和肠道微生物组的失调。鉴于微生物群、肠上皮细胞和免疫细胞之间的复杂相互作用,以及用于实验研究的胎儿人体组织的有限获取,动物模型长期以来一直是描述 NEC 机制的重要手段。然而,目前尚无完全模拟人类 NEC 的动物模型;此外,疾病机制似乎过于复杂,无法在单细胞培养中进行研究。因此,研究人员开发了新的方法,使肠上皮细胞暴露于环境和微生物因素的组合中,这些因素可能会引发 NEC。此外,类器官作为研究 NEC 发展的有前途的模型越来越受到关注。目前,已经提出了几种体外模型,并有助于更深入地描述该疾病。本文将提供对现有 NEC 体外模型的最新综述,并概述目前关于其分子基础的知识。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c4a/8268427/3e3ccc420797/ijms-22-06761-g001.jpg

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