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Stem Cells International
Volume 2016, Article ID 4370142, 16 pages
Research Article

Human Hepatocyte-Derived Induced Pluripotent Stem Cells: MYC Expression, Similarities to Human Germ Cell Tumors, and Safety Issues

1Pediatric Surgery Laboratory, Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland
2School of Life Sciences and “Frontiers in Genetics” National Program, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland
3Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland
4Division of Clinical Pathology, Geneva University Hospitals, 1211 Geneva, Switzerland

Received 5 July 2015; Accepted 26 November 2015

Academic Editor: Franca Fagioli

Copyright © 2016 Carmen Unzu et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Induced pluripotent stem cells (iPSC) are a most promising approach to the development of a hepatocyte transplantable mass sufficient to induce long-term correction of inherited liver metabolic diseases, thus avoiding liver transplantation. Their intrinsic self-renewal ability and potential to differentiate into any of the three germ layers identify iPSC as the most promising cell-based therapeutics, but also as drivers of tumor development. Teratoma development currently represents the gold standard to assess iPSC pluripotency. We analyzed the tumorigenic potential of iPSC generated from human hepatocytes (HEP-iPSC) and compared their immunohistochemical profiles to that of tumors developed from fibroblast and hematopoietic stem cell-derived iPSC. HEP-iPSC generated tumors significantly presented more malignant morphological features than reprogrammed fibroblasts or CD34+ iPSC. Moreover, the protooncogene myc showed the strongest expression in HEP-iPSC, compared to only faint expression in the other cell subsets. Random integration of transgenes and the use of potent protooncogenes such as myc might be a risk factor for malignant tumor development if hepatocytes are used for reprogramming. Nonviral vector delivery systems or reprogramming of cells obtained from less invasive harvesting methods would represent interesting options for future developments in stem cell-based approaches for liver metabolic diseases.