Kidney disease is a global health crisis affecting more than 850 million people worldwide. In the United States, annual Medicare expenditures for kidney disease and organ failure exceed $81 billion. Efforts to develop targeted therapeutics are limited by a poor understanding of the molecular mechanisms underlying human kidney disease onset and progression. Additionally, 90% of drug candidates fail in human clinical trials, often due to toxicity and efficacy not accurately predicted in animal models. The advent of ex vivo kidney models, such as those engineered from induced pluripotent stem (iPS) cells and organ-on-a-chip (organ-chip) systems, has garnered considerable interest owing to their ability to more accurately model tissue development and patient-specific responses and drug toxicity. This review describes recent advances in developing kidney organoids and organ-chips by harnessing iPS cell biology to model human-specific kidney functions and disease states. We also discuss challenges that must be overcome to realize the potential of organoids and organ-chips as dynamic and functional conduits of the human kidney. Achieving these technological advances could revolutionize personalized medicine applications and therapeutic discovery for kidney disease.

中文翻译：

---

使用类器官和芯片上的器官进行肾脏疾病建模


肾脏疾病是一种全球性健康危机，影响着全世界超过 8.5 亿人。在美国，每年用于肾脏疾病和器官衰竭的医疗保险支出超过 810 亿美元。由于对人类肾脏疾病发病和进展的分子机制了解不足，开发靶向治疗方法的努力受到限制。此外，90% 的候选药物在人体临床试验中失败，通常是由于在动物模型中未能准确预测毒性和功效。离体肾脏模型的出现，例如由诱导多能干细胞 (iPS) 和器官芯片 (器官芯片) 系统设计的模型，由于能够更准确地模拟组织发育和患者特异性反应和药物毒性。这篇综述介绍了通过利用 iPS 细胞生物学来模拟人类特定的肾脏功能和疾病状态来开发肾脏类器官和器官芯片的最新进展。我们还讨论了为了实现类器官和器官芯片作为人类肾脏的动态和功能性导管的潜力而必须克服的挑战。实现这些技术进步可能会彻底改变肾脏疾病的个性化医疗应用和治疗发现。