Dept of Molecular Pharmacology, University of Groningen, Groningen, The Netherlands
GRIAC Research Institute, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands.
Eur Respir Rev. 2021 Aug 3;30(161). doi: 10.1183/16000617.0042-2021. Print 2021 Sep 30.
Respiratory diseases are among the leading causes of morbidity and mortality worldwide, representing a major unmet medical need. New chemical entities rarely make it into the clinic to treat respiratory diseases, which is partially due to a lack of adequate predictive disease models and the limited availability of human lung tissues to model respiratory disease. Human pluripotent stem cells (hPSCs) may help fill this gap by serving as a scalable human model. In addition, human models of rare genetic mutations can be generated using hPSCs. hPSC-derived epithelial cells and organoids have already shown great potential for the understanding of disease mechanisms, for finding new potential targets by using high-throughput screening platforms, and for personalised treatments. These potentials can also be applied to other hPSC-derived lung cell types in the future. In this review, we will discuss how hPSCs have brought, and may continue to bring, major changes to the field of respiratory diseases by understanding the molecular mechanisms of the pathology and by finding efficient therapeutics.
呼吸系统疾病是全球发病率和死亡率的主要原因之一，这是未满足的主要医疗需求。很少有新的化学实体能进入临床用于治疗呼吸系统疾病，这部分是由于缺乏足够的预测疾病模型和有限的人类肺组织来模拟呼吸系统疾病。人类多能干细胞（hPSC）可以通过作为可扩展的人类模型来帮助填补这一空白。此外，还可以使用 hPSC 生成罕见遗传突变的人类模型。hPSC 衍生的上皮细胞和类器官已经显示出巨大的潜力，可用于了解疾病机制、通过高通量筛选平台寻找新的潜在靶点，以及用于个性化治疗。这些潜力将来也可应用于其他 hPSC 衍生的肺细胞类型。在这篇综述中，我们将讨论 hPSC 通过了解病理学的分子机制和寻找有效的治疗方法，如何为呼吸系统疾病领域带来并可能继续带来重大变化。
