title: Assessing the risks of genotoxicity in the therapeutic development of induced pluripotent stem cells.
abstract: Induced pluripotent stem cells (iPSCs) have great potential for regenerative medicine as well as for basic and translational research. However, following the initial excitement over the enormous prospects of this technology, several reports uncovered serious concerns regarding its safety for clinical applications and reproducibility for laboratory applications such as disease modeling or drug screening. In particular, the genomic integrity of iPSCs is the focus of extensive research. Epigenetic remodeling, aberrant expression of reprogramming factors, clonal selection, and prolonged in vitro culture are potential pathways for acquiring genomic alterations. In this review, we will critically discuss current reprogramming technologies particularly in the context of genotoxicity, and the consequences of these alternations for the potential applications of reprogrammed cells. In addition, current strategies of genetic modification of iPSCs, as well as applicable suicide strategies to control the risk of iPSC-based therapies will be introduced.
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: So Gun
authors.initials: SG
authors.lastname: Hong
authors.forename: Cynthia E
authors.initials: CE
authors.lastname: Dunbar
authors.forename: Thomas
authors.initials: T
authors.lastname: Winkler
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D065150:Cellular Reprogramming; D004249:DNA Damage; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D057890:Epigenomics; D018014:Gene Transfer Techniques; D041722:Genes, Transgenic, Suicide; D005822:Genetic Vectors; D023281:Genomics / Q000379:methods; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000637:transplantation*; D023421:Models, Animal; D044968:Regenerative Medicine; D015203:Reproducibility of Results; D012307:Risk Factors; D057170:Translational Research, Biomedical