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A Synthetic Hybrid Molecule for the Selective Removal of Human Pluripotent Stem Cells from Cell Mixtures
Author(s) -
Mao Di,
Ando Shin,
Sato Shinichi,
Qin Ying,
Hirata Nao,
Katsuda Yousuke,
Kawase Eihachiro,
Kuo TingFang,
Minami Itsunari,
Shiba Yuji,
Ueda Kazumitsu,
Nakatsuji Norio,
Uesugi Motonari
Publication year - 2017
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201610284
Subject(s) - induced pluripotent stem cell , chemistry , stem cell , efflux , cytotoxicity , small molecule , combinatorial chemistry , cell culture , selectivity , embryonic stem cell , biochemistry , in vitro , microbiology and biotechnology , biology , gene , genetics , catalysis
A major hurdle in stem cell therapy is the tumorigenic risk of residual undifferentiated stem cells. This report describes the design and evaluation of synthetic hybrid molecules that efficiently reduce the number of human induced pluripotent stem cells (hiPSCs) in cell mixtures. The design takes advantage of Kyoto probe 1 (KP‐1), a fluorescent chemical probe for hiPSCs, and clinically used anticancer drugs. Among the KP‐1–drug conjugates we synthesized, we found an exceptionally selective, chemically tractable molecule that induced the death of hiPSCs. Mechanistic analysis suggested that the high selectivity originates from the synergistic combination of transporter‐mediated efflux and the cytotoxicity mode of action. The present study offers a chemical and mechanistic rationale for designing selective, safe, and simple reagents for the preparation of non‐tumorigenic clinical samples.