Genetic and Epigenetic Instability of Human Pluripotent Stem Cells



Tung-Liang Chung, Nilay Y. Thakar, Ernst J. Wolvetang*
Stem Cell Engineering Group, Australian Institute for Bioengineering and Nanotechnology, Level 4, Building 75, University of Queensland, St Lucia QLD 4072 Australia


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Wolvetang et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the Stem Cell Engineering Group, Australian Institute for Bioengineering and Nanotechnology, Level 4, Building 75, University of Queensland, St Lucia QLD 4072 Australia e.wolvetang@uq.edu.au


Abstract

The preservation of the genetic and epigenetic integrity of human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) during 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 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 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 . 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.

Keywords: pluripotent stem cells , epigenetic , karyotype , induced pluripotent stem cells , aneuploid .