Mitigating the risk of tumor formation for human induced pluripotent stem cell-derived cellular products

Thursday, October 11, 2012 — Poster Session IV
2:00 p.m. – 4:00 p.m.	Natcher Conference Center, Building 45	FDA/CBER	STEMCELL-3

Authors

• W. Ou
• P. Li
• J. Reiser

Abstract

Human Induced Pluripotent Stem Cells (hiPSC) are very similar to human embryonic stem cells and have great potential for clinical applications. However, the current in vitro differentiation protocols are inefficient, resulting in a mixture of undifferentiated, partially differentiated and fully differentiated cells. Some of the partially differentiated cells may de-differentiate to become pluripotent cells. These undifferentiated and de-differentiated cells may form benign teratomas. On the other hand, genetic abnormalities pre-existing in the somatic cells used for reprogramming or caused by the reprogramming process itself may increase the risk of benign or malignant tumors. To address these problems, we used zinc finger nucleases to target a suicide gene, HSV1-TK, into the Oct4 locus, whose promoter is active in undifferentiated cells only. We isolated and characterized single cell clones. We plan to test the effects of depleting the undifferentiated cells using Ganciclovir (GCV) prior to engraftment on preventing teratoma formation and on engraftment efficiency. We will also engineer the TK gene into AAVS1 locus, a genomic safe harbor. In this case, all cells will express TK because the endogenous promoter is constitutive. We will test whether benign teratomas or malignant tumors that form after transplantation can be ablated with GCV.

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