Technology Development Division, BioMarin Pharmaceutical Inc, 105 Digital Drive, Novato, CA 94949, USA.
Institute of Neurophysiology and Center for Molecular Medicine, University of Cologne, Robert-Koch Str. 39, 50931 Cologne, Germany.
Cells. 2019 Apr 30;8(5):403. doi: 10.3390/cells8050403.
Induced pluripotent stem cell (iPSC)-based disease modelling and the cell replacement therapy approach have proven to be very powerful and instrumental in biomedical research and personalized regenerative medicine as evidenced in the past decade by unraveling novel pathological mechanisms of a multitude of monogenic diseases at the cellular level and the ongoing and emerging clinical trials with iPSC-derived cell products. iPSC-based disease modelling has sparked widespread enthusiasm and has presented an unprecedented opportunity in high throughput drug discovery platforms and safety pharmacology in association with three-dimensional multicellular organoids such as personalized organs-on-chips, gene/base editing, artificial intelligence and high throughput "omics" methodologies. This critical review summarizes the progress made in the past decade with the advent of iPSC discovery in biomedical applications and regenerative medicine with case examples and the current major challenges that need to be addressed to unleash the full potential of iPSCs in clinical settings and pharmacology for more effective and safer regenerative therapy.
基于诱导多能干细胞 (iPSC) 的疾病建模和细胞替代治疗方法已被证明在生物医学研究和个性化再生医学中非常强大和有效，这在过去十年中通过在细胞水平上揭示多种单基因疾病的新病理机制以及正在进行和新兴的 iPSC 衍生细胞产品临床试验得到了证明。基于 iPSC 的疾病建模激发了广泛的热情，并为高通量药物发现平台和安全药理学提供了前所未有的机会，与三维多细胞类器官（如个性化器官芯片）、基因/碱基编辑、人工智能和高通量“组学”方法相结合。这篇重要的综述总结了过去十年中随着 iPSC 在生物医学应用和再生医学中的发现所取得的进展，包括案例示例和当前需要解决的主要挑战，以释放 iPSC 在临床环境和药理学中用于更有效和更安全的再生治疗的全部潜力。
