Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.
Vascular Biology Program and Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
Nat Rev Gastroenterol Hepatol. 2024 Nov;21(11):751-773. doi: 10.1038/s41575-024-00968-3. Epub 2024 Aug 27.
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.
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，其中许多疾病受到微生物组、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与肠道健康和疾病相关的关键功能所必需的特征，例如消化或流体流动，以及来自微生物组、蠕动和免疫细胞的长期影响的贡献。在这里，我们回顾了由上皮细胞排列并与其他组织（如基质或内皮）接口的人类肠道器官上芯片（器官芯片）微流控培养模型的发展，这些组织可以经历流体流动和类似蠕动的运动。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提供了强大的建模方法，并且可以用于深入了解疾病的潜在分子和生物物理机制。它们还可以作为临床前工具，在相同的人类相关模型中发现新的药物，然后验证其治疗效果和安全性。
