Dissecting the Oncogenic and Tumorigenic Potential of Differentiated Human Induced Pluripotent Stem Cells and Human Embryonic Stem Cells

Departments of Medicine, Stanford University School of Medicine, Stanford, CA 94305-5454, USA.
Cancer Research (Impact Factor: 9.33). 06/2011; 71(14):5030-9. DOI: 10.1158/0008-5472.CAN-10-4402
Source: PubMed


Pluripotent stem cells, both human embryonic stem cells (hESC) and human-induced pluripotent stem cells (hiPSC), can give rise to multiple cell types and hence have tremendous potential for regenerative therapies. However, the tumorigenic potential of these cells remains a great concern, as reflected in the formation of teratomas by transplanted pluripotent cells. In clinical practice, most pluripotent cells will be differentiated into useful therapeutic cell types such as neuronal, cardiac, or endothelial cells prior to human transplantation, drastically reducing their tumorigenic potential. Our work investigated the extent to which these differentiated stem cell derivatives are truly devoid of oncogenic potential. In this study, we analyzed the gene expression patterns from three sets of hiPSC- and hESC-derivatives and the corresponding primary cells, and compared their transcriptomes with those of five different types of cancer. Our analysis revealed a significant gene expression overlap of the hiPSC- and hESC-derivatives with cancer, whereas the corresponding primary cells showed minimum overlap. Real-time quantitative PCR analysis of a set of cancer-related genes (selected on the basis of rigorous functional and pathway analyses) confirmed our results. Overall, our findings suggested that pluripotent stem cell derivatives may still bear oncogenic properties even after differentiation, and additional stringent functional assays to purify these cells should be done before they can be used for regenerative therapy.

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Available from: Joseph C Wu, Mar 23, 2015
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    • "The multilineage differentiation potential of hBSCs and the lack of tumor formation in recipient animals suggest the potential use of hBSCs as a therapeutic alternative to hESCs and hiPSCs, the use of which is hindered by ethical and safety issues [36, 44, 45]. Because of its ethical, noninvasive and plentiful nature, breastmilk offers a novel resource of patient-specific stem cells for applications in regenerative medicine. "
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    • "There are concerns with iPSCs regarding the use of the protooncogene c-myc, and insertion mutagenesis due to the use of retroviral sequences. There are also concerns regarding the tumourigenic potential of differentiated PSCs [31]. Additionally, there are issues surrounding the genetic and epigenetic integrity of the iPSCs and also the true nature of their immunogenic status. "
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