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

Paper ID Volume ID Publish Year Pages File Format Full-Text
6967 526 2012 10 PDF Available
Title
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. 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.

Keywords
Human induced pluripotent stem cells; Suicide gene; Thymidine kinase; NanoghiPSCs, Human induced pluripotent stem cells; hESCs, human embryonic stem cells; deltaTK, delta thymidine kinase; GCV, ganciclovir; EF1α, elongation factor 1α; bFGF, basic fibrobla
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Protecting against wayward human induced pluripotent stem cells with a suicide gene
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 33, Issue 11, April 2012, Pages 3195–3204
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us