Genova Elena, Cavion Federica, Lucafò Marianna, Leo Luigina De, Pelin Marco, Stocco Gabriele, Decorti Giuliana
PhD School in Reproduction and Development Sciences, University of Trieste, Trieste 34127, Italy.
Department of Life Sciences, University of Trieste, Trieste 34127, Italy.
World J Stem Cells. 2019 Dec 26;11(12):1020-1044. doi: 10.4252/wjsc.v11.i12.1020.
Adverse drug reactions (ADRs) are major clinical problems, particularly in special populations such as pediatric patients. Indeed, ADRs may be caused by a plethora of different drugs leading, in some cases, to hospitalization, disability or even death. In addition, pediatric patients may respond differently to drugs with respect to adults and may be prone to developing different kinds of ADRs, leading, in some cases, to more severe consequences. To improve the comprehension, and thus the prevention, of ADRs, the set-up of sensitive and personalized assays is urgently needed. Important progress is represented by the possibility of setting up groundbreaking patient-specific assays. This goal has been powerfully achieved using induced pluripotent stem cells (iPSCs). Due to their genetic and physiological species-specific differences and their ability to be differentiated ideally into all tissues of the human body, this model may be accurate in predicting drug toxicity, especially when this toxicity is related to individual genetic differences. This review is an up-to-date summary of the employment of iPSCs as a model to study ADRs, with particular attention to drugs used in the pediatric field. We especially focused on the intestinal, hepatic, pancreatic, renal, cardiac, and neuronal levels, also discussing progress in organoids creation. The latter are three-dimensional culture systems derived from pluripotent or adult stem cells simulating the architecture and functionality of native organs such as the intestine, liver, pancreas, kidney, heart, and brain. Based on the existing knowledge, these models are powerful and promising tools in multiple clinical applications including toxicity screening, disease modeling, personalized and regenerative medicine.
药物不良反应（ADR）是主要的临床问题，在儿科患者等特殊人群中尤为突出。事实上，多种不同药物都可能引发ADR，在某些情况下会导致住院、残疾甚至死亡。此外，儿科患者对药物的反应可能与成人不同，且更容易出现不同类型的ADR，在某些情况下会导致更严重的后果。为了更好地理解并预防ADR，迫切需要建立灵敏且个性化的检测方法。利用诱导多能干细胞（iPSC）建立具有开创性的患者特异性检测方法取得了重大进展。由于其遗传和生理上的物种特异性差异以及能够理想地分化为人体所有组织的能力，这种模型在预测药物毒性方面可能很准确，尤其是当这种毒性与个体遗传差异相关时。本综述是关于将iPSC用作研究ADR模型的最新总结，特别关注儿科领域使用的药物。我们尤其关注肠道、肝脏、胰腺、肾脏、心脏和神经层面，还讨论了类器官创建方面的进展。类器官是源自多能干细胞或成体干细胞的三维培养系统，模拟肠道、肝脏、胰腺、肾脏、心脏和大脑等天然器官的结构和功能。基于现有知识，这些模型在包括毒性筛查、疾病建模、个性化和再生医学在内的多种临床应用中是强大且有前景的工具。
