Genetic and Epigenetic Instability of Human Pluripotent Stem Cells

ABSTRACT

The preservation of the genetic and epigenetic integrity of human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) during in vitro propagation is critical for their use in both research and future therapeutic applications. It has been reported that hESCs and iPSCs have the ability to adapt to various culture conditions. However, human pluripotent stem cells cultured in serum free media can frequently accumulate point mutations, aneuploidy, and progressive epigenetic changes over prolonged culture in vitro for reasons that are poorly understood. The phenotypic and epigenetic changes brought about by the culture conditions can have significant impacts on their use in research and in clinical applications. An increased understanding of the potential effects of in vitro culture environments on pluripotent stem cell growth can enhance the development of improved culture systems for hESCs or iPSCs, and facilitate any future therapeutic applications using these cells. In this review, we first focus on the occurrence, potential causes and consequences of genetic and epigenetic unstable human pluripotent stem cells in vitro. We further discuss the current methods for detection and characterization of abnormal pluripotent stem cells that involve simply traditional karyotype analysis. All these observations highlight the need for novel screening strategies to determine the safety of hESCs or iPSCs and optimization and standardization of procedures for the generation and culture of pluripotent stem cells that minimize culture-induced epigenetic and genetic instability.

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