Chromosome Instability Of Mouse Induced Pluripotent Stem Cells In Prolonged Culture Process

Induced pluripotent cells (iPSCs) from terminally differentiated somatic cells have many therapeutic applications, particularly in the context of drug screening, in vitro disease modeling and cellular replacement therapies. However, various safety concerns still exist.Genetic instability of iPSCs in long-term culture process is a potential risk. In this study, we showed here chromosome instability existed in mouse iPSCs (miPSCs) in prolonged culture process, using cytogenetics methods such as metaphase spread and Fluorescent in situ hybridization (FISH). Incidence of chromosome numerical abnormality in miPSCs was high and frequency of Robertsonian translocation increased significantly along with the prolonged culture, in Yamanaka 4 factors induced mouse iPSCs rather than Yamanaka 3 factors induced mouse iPSCs. Additionally, cytokinesis-block micronucleus cytome (CBMN) assay indicated chromosome nondisjunction and translocation in mitosis contributed to high proportion of of miPSCs with chromosome 14 numerical abnormality and increased frequency of chromosome 14 Robertsonian translocation respectively.Our study provides a far-reaching implication that it's essential to improve iPSCs in-vitro culture conditions before iPSCs cell therapy.