Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA.
Department of Medicine, Western University, London, ON, Canada.
EMBO Mol Med. 2022 Nov 8;14(11):e13260. doi: 10.15252/emmm.202013260. Epub 2022 Oct 26.
Induced pluripotent stem cells (iPSCs) are a powerful modeling system for medical discovery and translational research. To date, most studies have focused on the potential for iPSCs for regenerative medicine, drug discovery, and disease modeling. However, iPSCs are also a powerful modeling system to investigate the effects of environmental exposure on the cardiovascular system. With the emergence of e-cigarettes, air pollution, marijuana use, opioids, and microplastics as novel cardiovascular risk factors, iPSCs have the potential for elucidating the effects of these toxins on the body using conventional two-dimensional (2D) arrays and more advanced tissue engineering approaches with organoid and other three-dimensional (3D) models. The effects of these environmental factors may be enhanced by genetic polymorphisms that make some individuals more susceptible to the effects of toxins. iPSC disease modeling may reveal important gene-environment interactions that exacerbate cardiovascular disease and predispose some individuals to adverse outcomes. Thus, iPSCs and gene-editing techniques could play a pivotal role in elucidating the mechanisms of gene-environment interactions and understanding individual variability in susceptibility to environmental effects.
诱导多能干细胞(iPSCs)是医学发现和转化研究的强大建模系统。迄今为止,大多数研究都集中在 iPSCs 在再生医学、药物发现和疾病建模方面的潜力上。然而,iPSCs 也是研究环境暴露对心血管系统影响的强大建模系统。随着电子烟、空气污染、大麻使用、阿片类药物和微塑料成为新的心血管危险因素的出现,iPSCs 有可能使用传统的二维(2D)阵列和更先进的组织工程方法(类器官和其他 3D 模型)来阐明这些毒素对身体的影响。这些环境因素的影响可能会因使某些个体更容易受到毒素影响的遗传多态性而增强。iPSC 疾病建模可能会揭示导致心血管疾病恶化并使某些个体易发生不良后果的重要基因-环境相互作用。因此,iPSCs 和基因编辑技术可以在阐明基因-环境相互作用的机制以及理解个体对环境影响的易感性的个体差异方面发挥关键作用。