Inhibition of an NAD+ Salvage Pathway Provides Efficient and Selective Toxicity to Human Pluripotent Stem Cells
Inhibition of an NAD+ Salvage Pathway Provides Efficient and Selective Toxicity to Human Pluripotent Stem Cells
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DOI：
10.5966/sctm.2014-0163
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发表时间：
2015-05-01
影响因子：
6
通讯作者：
Gundry, Rebekah L.
中科院分区：
文献类型：
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作者：
Kropp, Erin M.;Oleson, Bryndon J.;Gundry, Rebekah L.
人多能干细胞（hPSC）的致瘤潜力是hPSC衍生物在临床中广泛使用的主要限制。在这里，我们证明小分子STF-31在广泛的细胞培养条件下有效消除未分化的hPSC，与之前描述的靶向代谢过程的方法相比具有重要优势。尽管STF-31最初被描述为葡萄糖转运蛋白1的抑制剂，但这些数据支持将STF-31重新分类为通过抑制烟酰胺磷酸核糖基转移酶（NAMPT）的特异性NAD（+）补救途径抑制剂。这些发现证明了NAD（+）补救途径在hPSC生物学中的重要性，并描述了抑制NAMPT如何有效地从培养物中消除hPSC。这些结果将推进并加速安全、临床相关的hPSC衍生细胞疗法的开发。
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.