Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 21, 2021; 27(35): 5796-5802
Published online Sep 21, 2021. doi: 10.3748/wjg.v27.i35.5796
Induced pluripotent stem cells as an innovative model to study drug induced pancreatitis
Elena Genova, Gabriele Stocco, Giuliana Decorti
Elena Genova, Giuliana Decorti, Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Trieste 34137, Italy
Gabriele Stocco, Department of Life Sciences, University of Trieste, Trieste 34127, Italy
Giuliana Decorti, Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste 34127, Italy
Author contributions: Genova E, Stocco G and Decorti G designed the research study, reviewed and edited the manuscript; Genova E performed the research and wrote the manuscript; all authors have read and approved the final manuscript.
Supported by Italian Ministry of Health (IRCCS Burlo Garofolo), No. RC 7_2014.
Conflict-of-interest statement: Authors have nothing to disclose.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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: Giuliana Decorti, MD, Full Professor, Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Via dell’Istria 65, Trieste 34137, Italy. decorti@units.it
Received: March 17, 2021
Peer-review started: March 17, 2021
First decision: April 16, 2021
Revised: April 27, 2021
Accepted: August 30, 2021
Article in press: August 30, 2021
Published online: September 21, 2021

Drug-induced pancreatitis is a gastrointestinal adverse effect concerning about 2% of drugs. The majority of cases are mild to moderate but severe episodes can also occur, leading to hospitalization or even death. Unfortunately, the mechanisms of this adverse reaction are still not clear, hindering its prevention, and the majority of data available of this potentially life-threatening adverse effect are limited to case reports leading to a probable underestimation of this event. In particular, in this editorial, special attention is given to thiopurine-induced pancreatitis (TIP), an idiosyncratic adverse reaction affecting around 5% of inflammatory bowel disease (IBD) patients taking thiopurines as immunosuppressants, with a higher incidence in the pediatric population. Validated biomarkers are not available to assist clinicians in the prevention of TIP, also because of the inaccessibility of the pancreatic tissue, which limits the possibility to perform dedicated cellular and molecular studies. In this regard, induced pluripotent stem cells (iPSCs) and the exocrine pancreatic differentiated counterpart could be a great tool to investigate the cellular and molecular mechanisms underlying the development of this undesirable event. This particular type of stem cells is obtained by reprogramming adult cells, including fibroblasts and leukocytes, with a set of transcription factors known as the Yamanaka’s factors. Maintaining unaltered the donors’ genetic heritage, iPSCs represent an innovative model to study the mechanisms of adverse drug reactions in individual patients’ tissues not easily obtainable from human probands. Indeed, iPSCs can differentiate under adequate stimuli into almost any somatic lineage, opening a new world of opportunities for researchers. Several works are already available in the literature studying liver, central nervous system and cardiac cells derived from iPSCs and adverse drug effects. However, to our knowledge no studies have been performed on exocrine pancreas differentiated from iPSCs and drug-induced pancreatitis, so far. Hence, in this editorial we focus specifically on the description of the study of the mechanisms of TIP by using IBD patient-specific iPSCs and exocrine pancreatic differentiated cells as innovative in vitro models.

Keywords: Induced pluripotent stem cells, Therapy personalization, Patient-specific cells, Drug-induced pancreatitis, Thiopurines, Inflammatory bowel disease

Core Tip: About 5% of inflammatory bowel disease patients develop pancreatitis after thiopurine administration. The mechanism of this adverse effect is still not clear making it difficult to prevent. By differentiating induced pluripotent stem cells into their pancreatic exocrine counterpart, it is possible to set up innovative personalized in vitro models to study this adverse effect in a more effective way.