Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA.
Vascular Biology Program, Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
Nat Rev Genet. 2022 Aug;23(8):467-491. doi: 10.1038/s41576-022-00466-9. Epub 2022 Mar 25.
The failure of animal models to predict therapeutic responses in humans is a major problem that also brings into question their use for basic research. Organ-on-a-chip (organ chip) microfluidic devices lined with living cells cultured under fluid flow can recapitulate organ-level physiology and pathophysiology with high fidelity. Here, I review how single and multiple human organ chip systems have been used to model complex diseases and rare genetic disorders, to study host-microbiome interactions, to recapitulate whole-body inter-organ physiology and to reproduce human clinical responses to drugs, radiation, toxins and infectious pathogens. I also address the challenges that must be overcome for organ chips to be accepted by the pharmaceutical industry and regulatory agencies, as well as discuss recent advances in the field. It is evident that the use of human organ chips instead of animal models for drug development and as living avatars for personalized medicine is ever closer to realization.
动物模型未能预测人类的治疗反应是一个主要问题，这也使人们开始质疑它们在基础研究中的应用。带有活细胞的器官芯片（器官芯片）微流控装置在流体流动下培养，可以高度逼真地再现器官水平的生理学和病理生理学。在这里，我回顾了单个人类器官芯片系统和多个人类器官芯片系统如何用于模拟复杂疾病和罕见遗传疾病，研究宿主-微生物组相互作用，再现全身多器官生理学，以及重现人体对药物、辐射、毒素和传染性病原体的临床反应。我还讨论了器官芯片必须克服的挑战，以被制药行业和监管机构接受，并讨论了该领域的最新进展。显然，使用人类器官芯片代替动物模型进行药物开发，并作为个性化药物的活体替身，已经越来越接近现实。
