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肠类器官用于模拟肠道发育和疾病。

Intestinal organoids for modelling intestinal development and disease.

机构信息

Division of Cancer and Stem Cells, School of Medicine, Centre for Biomolecular Sciences, University of Nottingham, Nottingham NG7 2RD, UK.

Division of Cancer and Stem Cells, School of Medicine, Centre for Biomolecular Sciences, University of Nottingham, Nottingham NG7 2RD, UK

出版信息

Philos Trans R Soc Lond B Biol Sci. 2018 Jul 5;373(1750). doi: 10.1098/rstb.2017.0217.

DOI:10.1098/rstb.2017.0217
PMID:29786552
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5974440/
Abstract

Gastrointestinal diseases are becoming increasingly prevalent in developed countries. Immortalized cells and animal models have delivered important but limited insight into the mechanisms that initiate and propagate these diseases. Human-specific models of intestinal development and disease are desperately needed that can recapitulate structure and function of the gut Advances in pluripotent stem cells and primary tissue culture techniques have made it possible to culture intestinal epithelial cells in three dimensions that self-assemble to form 'intestinal organoids'. These organoids allow for new, human-specific models that can be used to gain insight into gastrointestinal disease and potentially deliver new therapies to treat them. Here we review current models of intestinal development and disease, considering where improvements could be made and potential future applications in the fields of developmental modelling, drug/toxicity testing and therapeutic uses.This article is part of the theme issue 'Designer human tissue: coming to a lab near you'.

摘要

在发达国家,胃肠道疾病的发病率越来越高。永生化细胞和动物模型为这些疾病的发病机制提供了重要但有限的认识。目前迫切需要能够重现肠道结构和功能的人类特异性肠道发育和疾病模型。多能干细胞和原代组织培养技术的进步使得在三维空间中培养肠上皮细胞并自我组装形成“肠类器官”成为可能。这些类器官为新的、具有人类特异性的模型提供了可能,可用于深入了解胃肠道疾病,并有可能为治疗这些疾病提供新的治疗方法。在这里,我们综述了目前的肠道发育和疾病模型,考虑了可以改进的地方,以及在发育模型、药物/毒性测试和治疗用途等领域的潜在未来应用。本文是“设计人类组织:就在你附近的实验室”主题特刊的一部分。

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本文引用的文献

1
Real-time Measurement of Epithelial Barrier Permeability in Human Intestinal Organoids.人肠道类器官上皮屏障通透性的实时测量
J Vis Exp. 2017 Dec 18(130):56960. doi: 10.3791/56960.
2
Intestinal Stem Cell Niche Insights Gathered from Both and Novel Models.从传统和新型模型中获得的肠道干细胞生态位见解
Stem Cells Int. 2017;2017:8387297. doi: 10.1155/2017/8387297. Epub 2017 Sep 7.
3
Generating CNS organoids from human induced pluripotent stem cells for modeling neurological disorders.利用人类诱导多能干细胞生成中枢神经系统类器官以模拟神经疾病。
Int J Physiol Pathophysiol Pharmacol. 2017 Jun 15;9(3):101-111. eCollection 2017.
4
Reconstruction of the mouse extrahepatic biliary tree using primary human extrahepatic cholangiocyte organoids.使用原代人肝外胆管细胞类器官重建小鼠肝外胆道系统。
Nat Med. 2017 Aug;23(8):954-963. doi: 10.1038/nm.4360. Epub 2017 Jul 3.
5
Stem Cells in Repair of Gastrointestinal Epithelia.干细胞在胃肠道上皮修复中的作用。
Physiology (Bethesda). 2017 Jul;32(4):278-289. doi: 10.1152/physiol.00005.2017.
6
Anomalous inferior mesenteric artery supplying the ascending, transverse, descending, and sigmoid colons.异常的肠系膜下动脉供应升结肠、横结肠、降结肠和乙状结肠。
Anat Sci Int. 2018 Jan;93(1):144-148. doi: 10.1007/s12565-017-0401-2. Epub 2017 Apr 6.
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Directed differentiation of human induced pluripotent stem cells into functional cholangiocyte-like cells.人诱导多能干细胞定向分化为功能性胆管细胞样细胞。
Nat Protoc. 2017 Apr;12(4):814-827. doi: 10.1038/nprot.2017.011. Epub 2017 Mar 23.
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Culture and establishment of self-renewing human and mouse adult liver and pancreas 3D organoids and their genetic manipulation.建立和培养人类和小鼠成人肝脏和胰腺 3D 类器官及其遗传操作。
Nat Protoc. 2016 Sep;11(9):1724-43. doi: 10.1038/nprot.2016.097. Epub 2016 Aug 25.