Lin Xiying, Tang Jiayu, Lou Yan-Ru
Department of Clinical Pharmacy and Drug Administration, School of Pharmacy, Fudan University, Shanghai 201203, China.
Pharmaceuticals (Basel). 2021 May 30;14(6):525. doi: 10.3390/ph14060525.
Human pluripotent stem cells (hPSCs), including human embryonic stem cells (hESCs) and human-induced pluripotent stem cells (hiPSCs), have the potential to accelerate the drug discovery and development process. In this review, by analyzing each stage of the drug discovery and development process, we identified the active role of hPSC-derived in vitro models in phenotypic screening, target-based screening, target validation, toxicology evaluation, precision medicine, clinical trial in a dish, and post-clinical studies. Patient-derived or genome-edited PSCs can generate valid in vitro models for dissecting disease mechanisms, discovering novel drug targets, screening drug candidates, and preclinically and post-clinically evaluating drug safety and efficacy. With the advances in modern biotechnologies and developmental biology, hPSC-derived in vitro models will hopefully improve the cost-effectiveness and the success rate of drug discovery and development.
人类多能干细胞（hPSC），包括人类胚胎干细胞（hESC）和人类诱导多能干细胞（hiPSC），具有加速药物发现和开发进程的潜力。在本综述中，通过分析药物发现和开发过程的各个阶段，我们确定了hPSC衍生的体外模型在表型筛选、基于靶点的筛选、靶点验证、毒理学评估、精准医学、盘中临床试验以及临床后研究中的积极作用。患者来源或基因组编辑的PSC可以生成有效的体外模型，用于剖析疾病机制、发现新的药物靶点、筛选候选药物以及在临床前和临床后评估药物的安全性和有效性。随着现代生物技术和发育生物学的进步，hPSC衍生的体外模型有望提高药物发现和开发的成本效益及成功率。
