Tissue Engineering and Regenerative Medicine, Northwick Park Institute for Medical Research (NPIMR), Harrow, London, HA1 3UJ, UK.
MRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, Merseyside, L69 3GE, UK.
J Appl Toxicol. 2019 Jan;39(1):4-15. doi: 10.1002/jat.3641. Epub 2018 Jun 11.
The gastrointestinal tract (GI) is a crucial part of the body for growth and development and its dysregulation can lead to several diseases with detrimental effects. Most of these diseases lack effective treatment, occurring as a result of inappropriate models to develop safe and potent therapies. Organoids are three-dimensional self-organizing and self-renewing structures that are composed of a cluster of different cells in vitro that resemble their organ of origin in architecture and function. Over recent years, organoids have been increasingly used to study developmental biology, disease progression, i.e., cancer, tissue engineering and regenerative medicine and other biological processes. Owing to their complex nature and ability to retain the morphological and molecular patterns of their tissue-of-origin, they have great potential as alternative tools/models for drug screening, development and biomarker discovery. Using a species with similar genetic homology to humans as a source of organoids, such as the porcine model may offer huge translational relevance. This review focuses on the culture and establishment of porcine organoid units and their potential use and application as in vitro models to further the science of drug discovery, by overcoming current limitations of established two- and three-dimensional models. It also highlights the translational application of using porcine organoids as a model of different disease contexts.
胃肠道（GI）是身体生长和发育的关键部分，其失调可导致几种疾病，产生有害影响。这些疾病大多缺乏有效治疗，这是由于缺乏开发安全有效疗法的合适模型所致。类器官是由体外一群不同细胞组成的三维自我组织和自我更新的结构，其在结构和功能上类似于其起源器官。近年来，类器官越来越多地被用于研究发育生物学、疾病进展（如癌症）、组织工程和再生医学以及其他生物学过程。由于其复杂的性质和保留其组织起源的形态和分子模式的能力，它们作为药物筛选、开发和生物标志物发现的替代工具/模型具有巨大的潜力。使用与人类具有相似遗传同源性的物种作为类器官的来源，如猪模型，可能具有巨大的转化相关性。本综述重点介绍了猪类器官单位的培养和建立，以及它们作为体外模型在药物发现科学中的潜在用途和应用，以克服现有二维和三维模型的局限性。它还强调了将猪类器官用作不同疾病背景模型的转化应用。
