A cell engineering strategy to enhance the safety of stem cell therapies

Elisa Oricchio, Eirini P. Papapetrou, Fabien Lafaille, Yosif M. Ganat, Sonja Kriks, Ana Ortega-Molina, Willie H. Mark, Julie Teruya-Feldstein, Jason T. Huse, Victor Reuter, Michel Sadelain, Lorenz Studer, Hans Guido Wendel

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

The long-term risk of malignancy associated with stem cell therapies is a significant concern in the clinical application of this exciting technology. We report a cancer-selective strategy to enhance the safety of stem cell therapies. Briefly, using a cell engineering approach, we show that aggressive cancers derived from human or murine induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs) are strikingly sensitive to temporary MYC blockade. On the other hand, differentiated tissues derived from human or mouse iPSCs can readily tolerate temporary MYC inactivation. In cancer cells, endogenous MYC is required to maintain the metabolic and epigenetic functions of the embryonic and cancer-specific pyruvate kinase M2 isoform (PKM2). In summary, our results implicate PKM2 in cancer's increased MYC dependence and indicate dominant MYC inhibition as a cancer-selective fail-safe for stem cell therapies.

Original languageEnglish
Pages (from-to)1677-1685
Number of pages9
JournalCell Reports
Volume8
Issue number6
DOIs
StatePublished - 25 Sep 2014

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