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
04/03/2015Pubmed ID
25834119Pubmed Central ID
PMC4414215DOI
10.5966/sctm.2014-0163Scopus ID
2-s2.0-84930445700 (requires institutional sign-in at Scopus site) 22 CitationsAbstract
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 RLAuthors
John A. Corbett PhD Chair, Professor in the Biochemistry department at Medical College of WisconsinNeil Hogg PhD Associate Dean, Professor in the Biophysics department at Medical College of Wisconsin
Daisy Sahoo PhD Dean, Professor in the Medicine department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
Cell Culture TechniquesCell Differentiation
Cytokines
Humans
NAD
Nicotinamide Phosphoribosyltransferase
Pluripotent Stem Cells
Pyridines
Signal Transduction
Small Molecule Libraries
