ArticlePloS one2013
Lentiviral vector mediated thymidine kinase expression in pluripotent stem cells enables removal of tumorigenic cells.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 20 citations in OpenAlex.
- Generation of therapeutic T cells from human induced pluripotent stem cells.Inflammation and regeneration · 2026Review
- Thymidylate synthase disruption to limit cell proliferation in cell therapies.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Engineered T cells from induced pluripotent stem cells: from research towards clinical implementation.Frontiers in immunology · 2023Review
- Efficient Genetic Safety Switches for Future Application of iPSC-Derived Cell Transplants.Journal of personalized medicine · 2021Article
- Elimination of proliferating cells from CNS grafts using a Ki67 promoter-driven thymidine kinase.Molecular therapy. Methods & clinical development · 2016Article
- Direct somatic lineage conversion.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2015Review
- A Safeguard System for Induced Pluripotent Stem Cell-Derived Rejuvenated T Cell Therapy.Stem cell reports · 2015Article
- Hepatocyte selection medium eliminating induced pluripotent stem cells among primary human hepatocytes.World journal of methodology · 2015Article
- An Inducible Caspase-9 Suicide Gene to Improve the Safety of Therapy Using Human Induced Pluripotent Stem Cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2015Article
- Stem cells: the pursuit of genomic stability.International journal of molecular sciences · 2014Review
- Inhibition of DNA topoisomerase II selectively reduces the threat of tumorigenicity following induced pluripotent stem cell-based myocardial therapy.Stem cells and development · 2014Article
- Development of an inducible caspase-9 safety switch for pluripotent stem cell-based therapies.Molecular therapy. Methods & clinical development · 2014Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Embryonic stem cells (ES) and induced pluripotent stem (iPS) cells represent promising tools for cell-based therapies and regenerative medicine. Nevertheless, implantation of ES cell derived differentiated cells holds the risk of teratoma formation due to residual undifferentiated cells. In order to tackle this problem, we used pluripotent stem cells consisting of ES and iPS cells of mouse genetically modified by lentiviral vectors (LVs) carrying herpes simplex virus thymidine kinase (HSV-TK) under the control of different promoters of pluripotency genes. Cells expressing TK in turn are eliminated upon administration of the prodrug ganciclovir (GCV). Our aim was to study the conditions required for a safe mechanism to clear residual undifferentiated cells but using low MOIs of lentiviruses to reduce the risk of insertional mutagenesis. Our in vitro data demonstrated that TK expression in pluripotent stem cells upon treatment with GCV led to elimination of undifferentiated cells. However, introduction of hygromycin resistance in the LV transduced ES cells followed by pre-selection with hygromycin and GCV treatment was required to abolish undifferentiated cells. Most importantly, transplantation of pre-selected ES cells that had been transduced with low MOI LV in mice resulted in no teratoma development after GCV treatment in vivo. Taken together, our data show that pre-selection of ES cells prior to in vivo application is necessary if vector integration events are minimized. The study presented here gives rise to safer use of pluripotent stem cells as promising cell sources in regenerative medicine in the future.
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