Inhibition of an NAD+ salvage pathway provides efficient and selective toxicity to human pluripotent stem cells

Erin M. Kropp, Bryndon J. Oleson, Katarzyna A. Broniowska, Subarna Bhattacharya, Alexandra C. Chadwick, Anne R. Diers, Qinghui Hu, Daisy Sahoo, Neil Hogg, Kenneth R. Boheler, John A. Corbett, Rebekah L. Gundry

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

The tumorigenic potential of human pluripotent stem cells (hPSCs) is a major limitation to the widespread use of hPSC derivatives in the clinic. Here, we demonstrate that the small molecule STF-31 is effective at eliminating undifferentiated hPSCs across a broad range of cell culture conditions with important advantages over previously described methods that target metabolic processes. Although STF-31 was originally described as an inhibitor of glucose transporter 1, these data support the reclas-sificationofSTF-31asaspecific NAD+ salvage pathway inhibitor through the inhibition ofnicotinamide phosphoribosyltransferase (NAMPT). These findings demonstrate the importanceofanNAD+ salvage pathway in hPSC biology and describe how inhibition of NAMPT can effectively eliminate hPSCs from culture. These results will advance and accelerate the development of safe, clinically relevant hPSC- derived cell-based therapies.

Original languageEnglish (US)
Pages (from-to)483-493
Number of pages11
JournalStem Cells Translational Medicine
Volume4
Issue number5
DOIs
StatePublished - Jan 1 2015

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Keywords

  • Human pluripotent stem cells
  • Metabolism
  • NAD
  • Salvage pathway
  • Selective toxicity

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

Cite this

Kropp, E. M., Oleson, B. J., Broniowska, K. A., Bhattacharya, S., Chadwick, A. C., Diers, A. R., Hu, Q., Sahoo, D., Hogg, N., Boheler, K. R., Corbett, J. A., & Gundry, R. L. (2015). Inhibition of an NAD+ salvage pathway provides efficient and selective toxicity to human pluripotent stem cells. Stem Cells Translational Medicine, 4(5), 483-493. https://doi.org/10.5966/sctm.2014-0163