Selective
Elimination of Human Pluripotent Stem Cells
by a Marine Natural Product Derivative
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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 <b>1</b>) 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