Organoids in gastrointestinal diseases: from experimental models to clinical translation.

Organoids in gastrointestinal diseases: from experimental models to clinical translation.
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DOI:
10.1136/gutjnl-2021-326560
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发表时间:
2022-09
期刊:
GUT
影响因子:
24.5
通讯作者:
Stappenbeck, Thaddeus S.
Stappenbeck, Thaddeus S.
中科院分区:
医学1区
文献类型:
--
作者:
Guenther, Claudia;Winner, Beate;Neurath, Markus F.;Stappenbeck, Thaddeus S.

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我们正在进入一个医学时代,在这个时代,我们将从患者那里获得越来越复杂的数据,以确定正确的诊断、预测结果和指导治疗。我们预测,最有价值的数据将由在时间和空间上都高度动态的系统产生。三维(3D)类器官有望成为治疗各种胃肠道疾病的极具价值的系统。在实验室中,类器官已经成为一个强大的系统,可以模拟分子和细胞过程,以非常详细的方式协调自然和病理生理的人体组织形成。临床前研究已经令人印象深刻地表明,这些培养皿中的器官可以利用患者来源的材料来模拟免疫、肿瘤、代谢或感染性胃肠道疾病。技术突破现在允许研究健康和疾病中的细胞通信和器官间串扰的分子机制,包括例如肠-脑轴或肠-肝轴上的通信。尽管在培养来自胃肠道不同部位的经典3D类器官方面取得了相当大的成功,但开发这些系统以最好地帮助患者仍然存在一些挑战。芯片上的器官、工程仿生系统(包括工程类器官)、微制造、生物打印以及增强的严谨性和可重复性等新平台将为组织工程以及再生和个性化医学开辟更好的途径。本文将重点介绍一些已建立的方法和一些令人兴奋的新观点在胃肠病学领域的类器官。目前,这一领域正准备向前发展,并以新的诊断和治疗方法的形式影响许多目前难治性胃肠道疾病。
We are entering an era of medicine where increasingly sophisticated data will be obtained from patients to determine proper diagnosis, predict outcomes and direct therapies. We predict that the most valuable data will be produced by systems that are highly dynamic in both time and space. Three-dimensional (3D) organoids are poised to be such a highly valuable system for a variety of gastrointestinal (GI) diseases. In the lab, organoids have emerged as powerful systems to model molecular and cellular processes orchestrating natural and pathophysiological human tissue formation in remarkable detail. Preclinical studies have impressively demonstrated that these organs-in-a-dish can be used to model immunological, neoplastic, metabolic or infectious GI disorders by taking advantage of patient-derived material. Technological breakthroughs now allow to study cellular communication and molecular mechanisms of interorgan cross-talk in health and disease including communication along for example, the gut–brain axis or gut–liver axis. Despite considerable success in culturing classical 3D organoids from various parts of the GI tract, some challenges remain to develop these systems to best help patients. Novel platforms such as organ-on-a-chip, engineered biomimetic systems including engineered organoids, micromanufacturing, bioprinting and enhanced rigour and reproducibility will open improved avenues for tissue engineering, as well as regenerative and personalised medicine. This review will highlight some of the established methods and also some exciting novel perspectives on organoids in the fields of gastroenterology. At present, this field is poised to move forward and impact many currently intractable GI diseases in the form of novel diagnostics and therapeutics.
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