Selective Elimination of Human Pluripotent Stem Cells by a Marine Natural Product Derivative

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• 作者：Ting-Fang Kuo ; Di Mao ; Nao Hirata ; Bilon Khambu ; Yasuhisa Kimura ; Eihachiro Kawase ; Hiroki Shimogawa ; Makoto Ojika ; Norio Nakatsuji ; Kazumitsu Ueda ; Motonari Uesugi
• 刊名：Journal of the American Chemical Society
• 出版年：2014
• 出版时间：July 16, 2014
• 年：2014
• 卷：136
• 期：28
• 页码：9798-9801
• 全文大小：302K
• ISSN：1520-5126

文摘

One of the current obstacles to stem cell therapy is the tumorigenic potential of residual undifferentiated stem cells. The present study reports rediscovery of a synthetic derivative of okadaic acid, a marine polyether toxin, as a reagent that selectively induces the death of human pluripotent stem cells. Cell-based screening of 333 cytotoxic compounds identified methyl 27-deoxy-27-oxookadaate (molecule 1) as a substrate of two ATP-binding cassette (ABC) transporters, ABCB1 (MDR1) and ABCG2 (BCRP), whose expression is repressed in human embryonic stem cells and induced pluripotent stem cells. The results demonstrate that selective elimination of human pluripotent stem cells can be achieved by designing cytotoxic small molecules with appropriate ABC-transporter selectivity.