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

Authors: Oricchio, E.; Papapetrou, E. P.; Lafaille, F.; Ganat, Y. M.; Kriks, S.; Ortega Molina, A.; Mark, W. H.; Teruya-Feldstein, J.; Huse, J. T.; Reuter, V.; Sadelain, M.; Studer, L.; Wendel, H. G.
Article Title: A cell engineering strategy to enhance the safety of stem cell therapies
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.
Journal Title: Cell Reports
Volume: 8
Issue: 6
ISSN: 2211-1247
Publisher: Cell Press  
Date Published: 2014-09-25
Start Page: 1677
End Page: 1685
Language: English
DOI: 10.1016/j.celrep.2014.08.039
PROVIDER: scopus
PMCID: PMC4177332
PUBMED: 25242333
Notes: Export Date: 3 November 2014 -- Source: Scopus
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MSK Authors
  1. Julie T Feldstein
    288 Feldstein
  2. Jason T Huse
    128 Huse
  3. Lorenz Studer
    159 Studer
  4. Sonja Kriks
    10 Kriks
  5. Michel W J Sadelain
    475 Sadelain
  6. Yosif Martin Ganat
    11 Ganat
  7. Willie Mark
    18 Mark
  8. Hans Guido Wendel
    64 Wendel
  9. Victor Reuter
    999 Reuter