Published online Oct 26, 2019. doi: 10.4252/wjsc.v11.i10.729
Peer-review started: March 15, 2019
First decision: June 5, 2019
Revised: June 13, 2019
Accepted: July 29, 2019
Article in press: July 29, 2019
Published online: October 26, 2019
Ten years after the initial generation of induced pluripotent stem cells (hiPSCs) from human tissues, their potential is no longer questioned, with over 15000 publications listed on PubMed, covering various fields of research; including disease modeling, cell therapy strategies, pharmacology/toxicology screening and 3D organoid systems. However, despite evidences that the presence of mutations in hiPSCs should be a concern, publications addressing genomic integrity of these cells represent less than 1% of the literature. After a first overview of the mutation types currently reported in hiPSCs, including karyotype abnormalities, copy number variations, single point mutation as well as uniparental disomy, this review will discuss the impact of reprogramming parameters such as starting cell type and reprogramming method on the maintenance of the cellular genomic integrity. Then, a specific focus will be placed on culture conditions and subsequent differentiation protocols and how their may also trigger genomic aberrations within the cell population of interest. Finally, in a last section, the impact of genomic alterations on the possible usages of hiPSCs and their derivatives will also be exemplified and discussed. We will also discuss which techniques or combination of techniques should be used to screen for genomic abnormalities with a particular focus on the necessary quality controls and the potential alternatives.
Core tip: The potential of human induced pluripotent stem cells (hiPSCs) is no longer questioned, with applications in many fields including disease modeling and cell therapy. However, the presence of mutations in hiPSCs is a concern. After a first overview of the mutation types currently reported in hiPSCs, this review is aimed at discussing the important points to understand and possibly control the occurrence of mutations during hiPSCs reprogramming, long term culture but also differentiation. Finally, the impact of genomic alterations on the possible usages of hiPSC derivatives will be discussed, with a focus on the necessary quality controls and the potential alternatives.