Protecting against wayward human induced pluripotent stem cells with a suicide gene

Abstract The generation of human induced pluripotent stem cells (hiPSCs) opens a prospect for regenerative medicine. However, transplantation of somatic cells derived from hiPSCs still harbor many risks such as cells’ incorrect differentiation or over-proliferation, and the worst, tumor formation. T...

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Bibliographic Details
Published in:Biomaterials 2012-04, Vol.33 (11), p.3195-3204
Main Authors: Cheng, Fuyi, Ke, Qiong, Chen, Fei, Cai, Bing, Gao, Yong, Ye, Chenghui, Wang, Ding, Zhang, Li, Lahn, Bruce T, Li, Weiqiang, Xiang, Andy Peng
Format: Article
Language:English
Subjects:
Advanced Basic Science
Animals
Apoptosis - genetics
Cell Survival - genetics
Cell Transformation, Neoplastic - genetics
Cell Transformation, Neoplastic - pathology
Cells, Cultured
Dentistry
Embryonic Stem Cells - cytology
Embryonic Stem Cells - physiology
Genes, Transgenic, Suicide - genetics
Genetic Enhancement - methods
Homeodomain Proteins - genetics
Human induced pluripotent stem cells
Humans
Mice
Mice, SCID
Nanog
Nanog Homeobox Protein
Suicide gene
Thymidine kinase
Thymidine Kinase - genetics
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Summary:Abstract The generation of human induced pluripotent stem cells (hiPSCs) opens a prospect for regenerative medicine. However, transplantation of somatic cells derived from hiPSCs still harbor many risks such as cells’ incorrect differentiation or over-proliferation, and the worst, tumor formation. Therefore, it’s essential to ravel out these obstacles before their clinical application. Herein, we genetically modified hiPSCs and human embryonic stem cells (hESCs) with a truncated herpes simplex virus delta thymidine kinase (deltaTK) gene driven by EF1α or Nanog promoter to selectively ablate wayward pluripotent stem cells. The results showed that insertion of deltaTK gene did not alter their pluripotency and self-renewal capacity but rendered them sensitive to ganciclovir, which induced elimination of deltaTK+ cells in vitro in a dose and time-dependent manner, most importantly, facilitated both prevention and ablation of tumors in vivo. Furthermore, comparative analysis between transduced hiPSCs and hESCs showed that there was no difference in ganciclovir sensitivity between them. This approach may help to develop safety strategies for clinical application of hiPSCs in regenerative medicine in the future.
ISSN:0142-9612
1878-5905
DOI:10.1016/j.biomaterials.2012.01.023