A Cell Engineering Strategy to Enhance the Safety of Stem Cell Therapies

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

来源：Cell Reports, 2014, 8(6): 1677-1685.

DOI：10.1016/j.celrep.2014.08.039

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.

• 出版日期2014-9-25