title: Selective elimination of human pluripotent stem cells by a marine natural product derivative.
abstract: 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.
authors.affiliation: Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University , Kyoto 606-8501, Japan.
authors.forename: Ting-Fang
authors.initials: TF
authors.lastname: Kuo
authors.forename: Di
authors.initials: D
authors.lastname: Mao
authors.forename: Nao
authors.initials: N
authors.lastname: Hirata
authors.forename: Bilon
authors.initials: B
authors.lastname: Khambu
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Kimura
authors.forename: Eihachiro
authors.initials: E
authors.lastname: Kawase
authors.forename: Hiroki
authors.initials: H
authors.lastname: Shimogawa
authors.forename: Makoto
authors.initials: M
authors.lastname: Ojika
authors.forename: Norio
authors.initials: N
authors.lastname: Nakatsuji
authors.forename: Kazumitsu
authors.initials: K
authors.lastname: Ueda
authors.forename: Motonari
authors.initials: M
authors.lastname: Uesugi
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors; D001688:Biological Products / Q000494:pharmacology*; D005456:Fluorescent Dyes; D006801:Humans; D009474:Neurons / Q000187:drug effects; D019319:Okadaic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*; D039904:Pluripotent Stem Cells / Q000187:drug effects*; D012235:Rhodamines / Q000737:chemistry*
chemical_list: D018528:ATP-Binding Cassette Transporters; D001688:Biological Products; D005456:Fluorescent Dyes; C000597746:Kyoto probe 1; D012235:Rhodamines; D019319:Okadaic Acid