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Inhibition of an NAD⁺ salvage pathway provides efficient and selective toxicity to human pluripotent stem cells. Stem Cells Transl Med 2015 May;4(5):483-93

Date

04/03/2015

Pubmed ID

25834119

Pubmed Central ID

PMC4414215

DOI

10.5966/sctm.2014-0163

Scopus ID

2-s2.0-84930445700   15 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 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.

Author List

Kropp EM, Oleson BJ, Broniowska KA, Bhattacharya S, Chadwick AC, Diers AR, Hu Q, Sahoo D, Hogg N, Boheler KR, Corbett JA, Gundry RL

Authors

John A. Corbett PhD Chair, Professor in the Biochemistry department at Medical College of Wisconsin
Neil Hogg PhD Associate Dean, Professor in the Biophysics department at Medical College of Wisconsin
Daisy Sahoo PhD Vice Chair, Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Cell Culture Techniques
Cell Differentiation
Cytokines
Humans
NAD
Nicotinamide Phosphoribosyltransferase
Pluripotent Stem Cells
Pyridines
Signal Transduction
Small Molecule Libraries