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: 9.28). 06/2011; 71(14):5030-9. DOI: 10.1158/0008-5472.CAN-10-4402
Source: PubMed

ABSTRACT 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.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Tissue Engineering and regenerative is aiming at generating tissues to replace damaged and deteriorated organs. Recently, tissue engineering was applied to generate artificial skin for burn patients, tissue engineered trachea, cartilage for knee-replacement procedures, urinary bladder, urethra substitutes and offered cellular therapies for the treatment of urinary incontinence. The major advantage of tissue engineering approach over traditional organ transplantation is to circumvent the problem of organ shortage. Tissues reconstructed from readily available patents' stem cells induced no immunogenicity when reimplanted in the patient. However, pluripotent stem cells are major limited factors in regenerating new tissues. To overcome these problems, we developed a new technology called as “invivo interspecies tissue engineering” (INVITE) and used the potential of induced pluripotent stem cells (iPSCs) to regenerate new tissues in a host organism. As a model, we used the mouse pluripotent stem cells to assess the potential of these cells to regenerate mouse tissues in rat. Three chimeric rats have been generated by mouse induced pluripotent stem cells assessed by monitoring of green fluorescence protein (GFP) and polymerase chain reaction (PCR) assays. This study shows clearly that mouse induced pluripotent stem cells are able to engraft in rat embryos and are capable to differentiate to multiple tissues. Beside the enormous important application of in vivo tissue engineering in human to develop new therapeutic approaches through regenerating new tissues, this model offers an accessible system for study of organ development and a valuable tool for personalized drug screening and a novel approach for personalized stem cell-based tissue regeneration.
    09/2014; DOI:10.1002/cbi3.10018
  • [Show abstract] [Hide abstract]
    ABSTRACT: A growing body of work has raised concern that many human pluripotent stem cell (hPSC) lines possess tumorigenic potential following differentiation to clinically relevant lineages. In this review, we highlight recent work characterizing the spectrum of cancer-like epigenetic derangements in human embryonic stem cells (hESC) and human induced pluripotent stem cells (hiPSC) that are associated with reprogramming errors or prolonged culture that may contribute to such tumorigenicity. These aberrations include cancer-like promoter DNA hypermethylation and histone marks associated with pluripotency, as well as aberrant X-chromosome regulation. We also feature recent work that suggests optimized high-fidelity reprogramming derivation methods can minimize cancer-associated epigenetic aberrations in hPSC, and thus ultimately improve the ultimate clinical utility of hiPSC in regenerative medicine.
    Current Opinion in Genetics & Development 10/2014; 28:43–49. DOI:10.1016/j.gde.2014.09.008 · 8.57 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The severely preterm infant receives a multitude of life-saving interventions, many of which carry risks of serious side effects. Cell therapy is an important and promising arm of regenerative medicine that may address a number of these problems. Most forms of cellular therapy use stem/progenitor cells or stem-like cells, which have the capacity to migrate, engraft and exert anti-inflammatory effects. Although some of these cell-based therapies have made their way to clinical trials in adults, little headway has been made in the neonatal patient group. This review discusses the efficacy of cell therapy in preclinical studies to date and their potential applications to diseases that afflict many prematurely born infants. Specifically, we identify the major hurdles that must be overcome before cell therapies can be safely used in the neonatal intensive care unit.
    Cytotherapy 12/2014; DOI:10.1016/j.jcyt.2014.06.004 · 3.10 Impact Factor

Full-text (2 Sources)

Available from
Mar 23, 2015