Consortium for Safety Assessment using Human iPS Cells (CSAHi), Japan.
Curr Pharm Biotechnol. 2020;21(9):807-828. doi: 10.2174/1389201021666200422090952.
Drug-induced toxicity remains one of the leading causes of discontinuation of the drug candidate and post-marketing withdrawal. Thus, early identification of the drug candidates with the potential for toxicity is crucial in the drug development process. With the recent discovery of human- Induced Pluripotent Stem Cells (iPSC) and the establishment of the differentiation protocol of human iPSC into the cell types of interest, the differentiated cells from human iPSC have garnered much attention because of their potential applicability in toxicity evaluation as well as drug screening, disease modeling and cell therapy. In this review, we expanded on current information regarding the feasibility of human iPSC-derived cells for the evaluation of drug-induced toxicity with a focus on human iPSCderived hepatocyte (iPSC-Hep), cardiomyocyte (iPSC-CMs) and neurons (iPSC-Neurons). Further, we CSAHi, Consortium for Safety Assessment using Human iPS Cells, reported our gene expression profiling data with DNA microarray using commercially available human iPSC-derived cells (iPSC-Hep, iPSC-CMs, iPSC-Neurons), their relevant human tissues and primary cultured human cells to discuss the future direction of the three types of human iPSC-derived cells.
药物诱导的毒性仍然是导致候选药物停药和上市后撤市的主要原因之一。因此,在药物开发过程中,早期识别有潜在毒性的候选药物至关重要。随着人类诱导多能干细胞(iPSC)的最新发现和人类 iPSC 向感兴趣的细胞类型分化的方案的建立,人类 iPSC 分化而来的细胞因其在毒性评估以及药物筛选、疾病建模和细胞治疗中的潜在应用而备受关注。在这篇综述中,我们扩展了目前关于人类 iPSC 衍生细胞在药物诱导毒性评估中的可行性的信息,重点介绍了人类 iPSC 衍生的肝细胞(iPSC-Hep)、心肌细胞(iPSC-CMs)和神经元(iPSC-Neurons)。此外,我们还报告了使用商用的人类 iPSC 衍生细胞(iPSC-Hep、iPSC-CMs、iPSC-Neurons)、其相关的人类组织和原代培养的人类细胞进行 DNA 微阵列的基因表达谱分析数据,以讨论三种类型的人类 iPSC 衍生细胞的未来方向。