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Int. J. Mol. Sci. 2018, 19(1), 197; https://doi.org/10.3390/ijms19010197

Introduction of Exogenous HSV-TK Suicide Gene Increases Safety of Keratinocyte-Derived Induced Pluripotent Stem Cells by Providing Genetic “Emergency Exit” Switch

Department of Transplantation, Faculty of Clinical Immunology and Transplantation, Institute of Pediatrics, Collegium Medicum Jagiellonian University, Wielicka 265, 30-663 Kraków, Poland
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Received: 7 December 2017 / Revised: 3 January 2018 / Accepted: 5 January 2018 / Published: 9 January 2018
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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Abstract

Since their invention in 2006, induced Pluripotent Stem (iPS) cells remain a great promise for regenerative medicine circumventing the ethical issues linked to Embryonic Stem (ES) cell research. iPS cells can be generated in a patient-specific manner as an unlimited source of various cell types for in vitro drug screening, developmental biology studies and regenerative use. Having the capacity of differentiating into the cells of all three primary germ layers, iPS cells have high potential to form teratoma tumors. This remains their main disadvantage and hazard which, until resolved, prevents utilization of iPS cells in clinic. Here, we present an approach for increasing iPS cells safety by introducing genetic modification—exogenous suicide gene Herpes Simplex Virus Thymidine Kinase (HSV-TK). Its expression results in specific vulnerability of genetically modified cells to prodrug—ganciclovir (GCV). We show that HSV-TK expressing cells can be eradicated both in vitro and in vivo with high specificity and efficiency with low doses of GCV. Described strategy increases iPS cells safety for future clinical applications by generating “emergency exit” switch allowing eradication of transplanted cells in case of their malfunction. View Full-Text
Keywords: induced Pluripotent Stem (iPS); suicide gene therapy; genetic safeguarding induced Pluripotent Stem (iPS); suicide gene therapy; genetic safeguarding
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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. (CC BY 4.0).

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Sułkowski, M.; Konieczny, P.; Chlebanowska, P.; Majka, M. Introduction of Exogenous HSV-TK Suicide Gene Increases Safety of Keratinocyte-Derived Induced Pluripotent Stem Cells by Providing Genetic “Emergency Exit” Switch. Int. J. Mol. Sci. 2018, 19, 197.

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