Journal article

Identification of Unsafe Human Induced Pluripotent Stem Cell Lines Using a Robust Surrogate Assay for Pluripotency

Juan Carlos Polanco, Mirabelle SH Ho, Bei Wang, Qi Zhou, Ernst Wolvetang, Elizabeth Mason, Christine A Wells, Gabriel Kolle, Sean M Grimmond, Ivan Bertoncello, Carmel O'Brien, Andrew L Laslett

STEM CELLS | WILEY | Published : 2013

Abstract

Human induced pluripotent stem cells (hiPSC) have the potential to generate healthy cells and tissues for the study and medical treatment of a large number of diseases. The utility of putative hiPSC-based therapies is constrained by a lack of robust quality-control assays that address the stability of the cells or their capacity to form teratomas after differentiation. Here we report that virally derived hiPSC, but not human embryonic stem cells (hESC) or hiPSC derived using episomal nonintegrating vectors, exhibit a propensity to revert to a pluripotent phenotype following differentiation. This instability was revealed using our published method to identify pluripotent cells undergoing very..

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Grants

Funding Acknowledgements

We thank the StemCore facility at Monash University for provision of hPSC lines, the SRC microarray facility at the University of Queensland for processing Illumina microarrays, the Flow-Core facility at Monash University for FACS services. Human iPS cell lines (hiPS-IMR90 and hiPS-Foreskin) were kindly provided by Dr. James A. Thomson (University of Wisconsin). NOD/SCID IL2R gamma<SUP>-/-</SUP> mice were generously provided by Dr. Susie Nilsson at CSIRO. We also thank Chad Heazlewood and Daniela Cardozo at CSIRO for technical assistance with histology and mouse work and the following for critical appraisals of draft versions of this manuscript; David Haylock and Tung-Liang Chung (CSIRO), Martin Pera (University of Melbourne) and Jose Polo (Monash University). GCTM-2 and TG30 were kindly supplied by Prof. Martin Pera (University of Melbourne). This work was supported by research grants from the Australian Stem Cell Centre and the New South Wales and Victorian Government Stem Cell Research Grant Program to A. L. L. A. L. L. is a Partner Investigator on the Australian Research Council (ARC) Special Research Initiative in Stem Cell Science, Stem Cells Australia.