Piersma Aldert H, Baker Nancy C, Daston George P, Flick Burkhard, Fujiwara Michio, Knudsen Thomas B, Spielmann Horst, Suzuki Noriyuki, Tsaioun Katya, Kojima Hajime
Center for Health Protection, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
Leidos, Research Triangle Park, NC, USA.
Curr Res Toxicol. 2022 May 13;3:100074. doi: 10.1016/j.crtox.2022.100074. eCollection 2022.
This manuscript provides a review focused on embryonic stem cell-based models and their place within the landscape of alternative developmental toxicity assays. Against the background of the principles of developmental toxicology, the wide diversity of alternative methods using pluripotent stem cells developed in this area over the past half century is reviewed. In order to provide an overview of available models, a systematic scoping review was conducted following a published protocol with inclusion criteria, which were applied to select the assays. Critical aspects including biological domain, readout endpoint, availability of standardized protocols, chemical domain, reproducibility and predictive power of each assay are described in detail, in order to review the applicability and limitations of the platform in general and progress moving forward to implementation. The horizon of innovative routes of promoting regulatory implementation of alternative methods is scanned, and recommendations for further work are given.
本手稿提供了一篇综述，重点关注基于胚胎干细胞的模型及其在替代发育毒性试验领域中的地位。在发育毒理学原理的背景下，回顾了过去半个世纪该领域开发的使用多能干细胞的多种替代方法。为了概述现有模型，按照已发表的方案及纳入标准进行了系统的范围综述，这些标准用于选择试验。详细描述了每个试验的关键方面，包括生物学领域、读出终点、标准化方案的可用性、化学领域、可重复性和预测能力，以便总体上回顾该平台的适用性和局限性以及未来实施方面的进展。审视了促进替代方法监管实施的创新途径，并给出了进一步工作的建议。
