Institute for Regenerative Medicine, University of Zurich, Zurich, Switzerland.
Wyss Translational Center Zurich, Zurich, Switzerland.
Clin Pharmacol Ther. 2019 Jan;105(1):79-85. doi: 10.1002/cpt.1286. Epub 2018 Dec 21.
Human cardiac drug discovery and disease modeling face challenges in recapitulating cellular complexity and animal-to-human translation due to the limitations of conventional 2D cell culture and animal models. The development of human cardiac organoid technologies could help in stimulating and maintaining differentiated cell functions for extended periods of time. By closely mimicking in vivo organ functions in vitro they could thereby help in overcoming the obstacles mentioned above. Through the construction of human cardiac organoids from pluripotent stem cell-derived cells, derived from patients with specific known genotypes and phenotypes, more complex and robust in vitro tools have recently become available for disease modeling. In this review, we will describe the relevance and importance of evolving organoid platforms in disease biology. We further provide examples of cardiac organoid platforms, which may lead the way toward future personalized medicine and drug discovery.
人类心脏的药物发现和疾病建模在细胞复杂性和动物到人类的转化方面面临挑战,这是由于传统的 2D 细胞培养和动物模型的局限性所致。人类心脏类器官技术的发展有助于刺激和维持分化细胞的功能,使其能够长时间保持分化状态。通过在体外模拟体内器官的功能,它们可以帮助克服上述障碍。通过从多能干细胞衍生的细胞构建来自特定已知基因型和表型的患者的人类心脏类器官,最近已经有了更复杂和更强大的疾病建模体外工具。在这篇综述中,我们将描述进化中的类器官平台在疾病生物学中的相关性和重要性。我们进一步提供了心脏类器官平台的例子,这些例子可能为未来的个性化医学和药物发现铺平道路。