Induced pluripotent stem cells for therapy personalization in pediatric patients:Focus on drug-induced adverse events  

作　　者：Elena Genova Federica Cavion Marianna Lucafò Luigina De Leo Marco Pelin Gabriele Stocco Giuliana Decorti 

机构地区：[1]PhD School in Reproduction and Development Sciences,University of Trieste,Trieste 34127,Italy [2]Department of Life Sciences,University of Trieste,Trieste 34127,Italy [3]Institute for Maternal and Child Health,IRCCS Burlo Garofolo,Trieste 34137,Italy [4]Department of Medical,Surgical and Health Sciences,University of Trieste,Trieste 34127,Italy

出　　处：《World Journal of Stem Cells》2019年第12期1020-1044,共25页世界干细胞杂志（英文版）（电子版）

基　　金：Supported by Italian Ministry of Health(IRCCS Burlo Garofolo),No.RC 7_2014,No.RC 10_2019;progetto fondo di ricerca Ateneo,Universitàdi Trieste,No.FRA2018

摘　　要：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 in vitro 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.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 in vitro 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.

关 键 词：Induced PLURIPOTENT stem cells ORGANOIDS Adverse drug reactions Intestinal TOXICITY Hepatic TOXICITY Pancreatic TOXICITY NEPHROTOXICITY CARDIOTOXICITY Neurotoxicity 

分 类 号：R97[医药卫生—药品]