Review
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Dec 26, 2019; 11(12): 1020-1044
Published online Dec 26, 2019. doi: 10.4252/wjsc.v11.i12.1020
Induced pluripotent stem cells for therapy personalization in pediatric patients: Focus on drug-induced adverse events
Elena Genova, Federica Cavion, Marianna Lucafò, Luigina De Leo, Marco Pelin, Gabriele Stocco, Giuliana Decorti
Elena Genova, PhD School in Reproduction and Development Sciences, University of Trieste, Trieste 34127, Italy
Federica Cavion, Marco Pelin, Gabriele Stocco, Department of Life Sciences, University of Trieste, Trieste 34127, Italy
Marianna Lucafò, Luigina De Leo, Giuliana Decorti, Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Trieste 34137, Italy
Giuliana Decorti, Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste 34127, Italy
Author contributions: The authors contributed equally to this work in all aspects.
Supported by Italian Ministry of Health (IRCCS Burlo Garofolo), No. RC 7_2014, No. RC 10_2019; progetto fondo di ricerca Ateneo, Università di Trieste, No. FRA2018
Conflict-of-interest statement: Authors of this manuscript have no conflicts of interest to disclose.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Gabriele Stocco, PhD, Assistant Professor, Department of Life Sciences, University of Trieste, via Fleming 22, Trieste 34127, Italy. stoccog@units.it
Telephone: +39-40-5588634
Received: March 23, 2019
Peer-review started: March 26, 2019
First decision: August 1,2019
Revised: September 5, 2019
Accepted: October 14, 2019
Article in press: October 14, 2019
Published online: December 26, 2019
Processing time: 250 Days and 15.5 Hours
Abstract

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.

Keywords: Induced pluripotent stem cells; Organoids; Adverse drug reactions; Intestinal toxicity; Hepatic toxicity; Pancreatic toxicity; Nephrotoxicity; Cardiotoxicity; Neurotoxicity

Core tip: Adverse drug reactions (ADRs) are major clinical problems, especially in pediatric patients, who may respond differently to drugs with respect to adults. This up-to-date review focuses on the employment of patient-derived induced pluripotent stem cells and related systems (i.e. stem cell-derived organoids) to study ADRs in adults, and wherever available, in the pediatric field. We especially focused on the intestinal, hepatic, pancreatic, renal, cardiac, and neuronal levels, in which the major ADRs are usually observed. Due to their genetic and physiological species-specific differences, these models may be accurate in predicting drug toxicity.