Nature Reviews Gastroenterology & Hepatology ( IF 45.9 ) Pub Date : 2024-08-27 , DOI: 10.1038/s41575-024-00968-3 Alican Özkan 1 , Nina Teresa LoGrande 1 , Jessica F Feitor 1 , Girija Goyal 1 , Donald E Ingber 1, 2, 3
Alterations in intestinal structure, mechanics and physiology underlie acute and chronic intestinal conditions, many of which are influenced by dysregulation of microbiome, peristalsis, stroma or immune responses. Studying human intestinal physiology or pathophysiology is difficult in preclinical animal models because their microbiomes and immune systems differ from those of humans. Although advances in organoid culture partially overcome this challenge, intestinal organoids still lack crucial features that are necessary to study functions central to intestinal health and disease, such as digestion or fluid flow, as well as contributions from long-term effects of living microbiome, peristalsis and immune cells. Here, we review developments in organ-on-a-chip (organ chip) microfluidic culture models of the human intestine that are lined by epithelial cells and interfaced with other tissues (such as stroma or endothelium), which can experience both fluid flow and peristalsis-like motions. Organ chips offer powerful ways to model intestinal physiology and disease states for various human populations and individual patients, and can be used to gain new insight into underlying molecular and biophysical mechanisms of disease. They can also be used as preclinical tools to discover new drugs and then validate their therapeutic efficacy and safety in the same human-relevant model.
中文翻译:
用于疾病建模和个性化医疗的肠道器官芯片
肠道结构、力学和生理学的改变是急性和慢性肠道疾病的基础,其中许多受到微生物组、蠕动、基质或免疫反应失调的影响。在临床前动物模型中研究人类肠道生理学或病理生理学很困难,因为它们的微生物组和免疫系统与人类不同。尽管类器官培养的进步部分克服了这一挑战,但肠道类器官仍然缺乏研究肠道健康和疾病核心功能所必需的关键特征,例如消化或液体流动,以及活微生物组、蠕动和免疫细胞的长期影响的贡献。在这里,我们回顾了人类肠道器官芯片(器官芯片)微流控培养模型的发展,该模型由上皮细胞排列并与其他组织(如基质或内皮细胞)接触,这些组织可以经历液体流动和蠕动样运动。器官芯片为各种人群和个体患者的肠道生理学和疾病状态建模提供了强大的方法,可用于获得对疾病潜在分子和生物物理机制的新见解。它们还可以用作临床前工具来发现新药,然后在相同的人类相关模型中验证其治疗效果和安全性。