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Biomaterials. 2012 Oct;33(29):7261-71. doi: 10.1016/j.biomaterials.2012.06.038. Epub 2012 Jul 12.

Safeguarding pluripotent stem cells for cell therapy with a non-viral, non-integrating episomal suicide construct.

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  • 1Wake Forest Institute for Regenerative Medicine, Wake Forest University Health Sciences, Winston-Salem, NC 27157, USA.


Pluripotent stem cells provide an unlimited cell source for cell therapy. However, residual pluripotent stem cells after differentiation can form tumors. Modifying stem cells with suicide constructs through integrating plasmid DNA and viral vectors has been attempted to specifically eliminate residual pluripotent stem cells after differentiation. However, integration of foreign DNA has the potential of insertional mutagenesis, position effects and silencing. Scaffold/matrix attachment region (S/MAR)-based plasmid DNA can be maintained extra-chromosomally, offering a safer alternative to integrating vectors for this purpose. Here, we report the design of an S/MAR-based suicide construct capable of episomal maintenance and specifically killing pluripotent stem cells but not differentiated cells in the presence of ganciclovir. Treating cells differentiated from episomal suicide construct-modified stem cells with ganciclovir reduces the tumor formation risk after cell transplantation. Tumors formed by such modified pluripotent stem cells could be inhibited by ganciclovir administration. This episomal suicide construct enables negative selection of residual pluripotent stem cells in vitro and control of tumors formed from residual pluripotent stem cells in vivo.

Copyright © 2012 Elsevier Ltd. All rights reserved.

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