Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Eur Heart J. 2024 Oct 21;45(40):4275-4290. doi: 10.1093/eurheartj/ehae519.
Cardiovascular diseases persist as a global health challenge that requires methodological innovation for effective drug development. Conventional pipelines relying on animal models suffer from high failure rates due to significant interspecies variation between humans and animal models. In response, the recently enacted Food and Drug Administration Modernization Act 2.0 encourages alternative approaches including induced pluripotent stem cells (iPSCs). Human iPSCs provide a patient-specific, precise, and screenable platform for drug testing, paving the way for cardiovascular precision medicine. This review discusses milestones in iPSC differentiation and their applications from disease modelling to drug discovery in cardiovascular medicine. It then explores challenges and emerging opportunities for the implementation of 'clinical trials in-a-dish'. Concluding, this review proposes a framework for future clinical trial design with strategic incorporations of iPSC technology, microphysiological systems, clinical pan-omics, and artificial intelligence to improve success rates and advance cardiovascular healthcare.
心血管疾病仍然是一个全球性的健康挑战，需要方法学创新来有效开发药物。传统的依赖动物模型的管道由于人类和动物模型之间存在显著的种间差异，因此失败率很高。有鉴于此，最近颁布的《食品和药物管理局现代化法案 2.0》鼓励采用替代方法，包括诱导多能干细胞 (iPSC)。人类 iPSC 为药物测试提供了一个患者特异性、精确性和可筛选的平台，为心血管精准医学铺平了道路。本文综述了 iPSC 分化的里程碑及其在心血管医学中从疾病建模到药物发现的应用。然后探讨了“在盘中进行临床试验”的实施所面临的挑战和新兴机遇。最后，本文提出了一个未来临床试验设计的框架，战略性地纳入 iPSC 技术、微生理系统、临床 pan-omics 和人工智能，以提高成功率并推进心血管医疗保健。
