Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, North Carolina, USA; email:
Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA.
Annu Rev Biomed Eng. 2024 Jul;26(1):383-414. doi: 10.1146/annurev-bioeng-072623-044010. Epub 2024 Jun 20.
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.
肾脏疾病是全球范围内的一个健康危机，影响着全球超过 8.5 亿人。在美国，肾脏疾病和器官衰竭的年度医疗保险支出超过 810 亿美元。由于对人类肾脏疾病发病和进展的分子机制缺乏深入了解，针对特定疗法的研发工作受到限制。此外，90%的药物候选物在人体临床试验中失败，这通常是由于毒性和疗效在动物模型中无法准确预测。体外肾脏模型的出现，如诱导多能干细胞（iPS）和器官芯片（organ-chip）系统工程化的模型，由于其能够更准确地模拟组织发育和患者特异性反应以及药物毒性，因此引起了广泛关注。本综述描述了利用 iPS 细胞生物学开发肾脏类器官和器官芯片的最新进展，以模拟人类特异性肾脏功能和疾病状态。我们还讨论了必须克服的挑战，以实现类器官和器官芯片作为人类肾脏动态和功能导管的潜力。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。
