Journal
CELL CHEMICAL BIOLOGY
Volume 24, Issue 6, Pages 685-+Publisher
CELL PRESS
DOI: 10.1016/j.chembiol.2017.04.010
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Funding
- JSPS KAKENHI [15H05722]
- Research Center Network for the Realization of Regenerative Medicine
- Human Frontier Science Program and Schlumberger's Faculty
- Grants-in-Aid for Scientific Research [15H05722] Funding Source: KAKEN
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The incomplete differentiation of human induced pluripotent stem cells (iPSCs) poses a serious safety risk owing to their potential tumorigenicity, hindering their clinical application. Here, we explored the potential of phospho-D-peptides as novel iPSC-eliminating agents. Alkaline phosphatases overexpressed on iPSCs dephosphorylate phospho-D-peptides into hydrophobic peptides that aggregate and induce cell death. We isolated a peptide candidate, D-3, that selectively and rapidly induced toxicity in iPSCs within 1 hr but had little influence on various non-iPSCs, including primary hepatocytes and iPSC-derived cardiomyocytes. Two hours of D-3 treatment efficiently eliminated iPSCs from both single cultures and co-cultures spiked with increasing ratios of iPSCs. In addition, D-3 prevented residual iPSC-induced teratoma formation in a mouse tumorigenicity assay. These results suggest the enormous potential of D-3 as a low-cost and effective anti-iPSC agent for both laboratory use and for the safe clinical application of iPSC-derived cells in regenerative medicine.
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