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Stem Cells Transl Med. 2015 May;4(5):483-93. doi: 10.5966/sctm.2014-0163. Epub 2015 Apr 1.

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

Author information

1
Department of Biochemistry, Department of Biophysics, Redox Biology Program, and Department of Medicine, Division of Endocrinology, Metabolism and Clinical Nutrition, Medical College of Wisconsin, Milwaukee, Wisconsin, USA; Department of Physiology, Stem Cell and Regenerative Medicine Consortium, Li Ka Shing Faculty of Medicine, Hong Kong University, Hong Kong, Special Administrative Region of the People's Republic of China; Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
2
Department of Biochemistry, Department of Biophysics, Redox Biology Program, and Department of Medicine, Division of Endocrinology, Metabolism and Clinical Nutrition, Medical College of Wisconsin, Milwaukee, Wisconsin, USA; Department of Physiology, Stem Cell and Regenerative Medicine Consortium, Li Ka Shing Faculty of Medicine, Hong Kong University, Hong Kong, Special Administrative Region of the People's Republic of China; Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA rgundry@mcw.edu.

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 reclassification of STF-31 as a specific NAD⁺ salvage pathway inhibitor through the inhibition of nicotinamide phosphoribosyltransferase (NAMPT). These findings demonstrate the importance of an NAD⁺ 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.

KEYWORDS:

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

PMID:
25834119
PMCID:
PMC4414215
DOI:
10.5966/sctm.2014-0163
[Indexed for MEDLINE]
Free PMC Article

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