2017年2月
A Synthetic Hybrid Molecule for the Selective Removal of Human Pluripotent Stem Cells from Cell Mixtures
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
- 巻
- 56
- 号
- 7
- 開始ページ
- 1765
- 終了ページ
- 1770
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1002/anie.201610284
- 出版者・発行元
- WILEY-V C H VERLAG GMBH
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 probe1 (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.
- リンク情報
- ID情報
-
- DOI : 10.1002/anie.201610284
- ISSN : 1433-7851
- eISSN : 1521-3773
- PubMed ID : 28067441
- Web of Science ID : WOS:000395554900008