Efficient, Selective Removal of Human Pluripotent Stem Cells via Ecto-Alkaline Phosphatase-Mediated Aggregation of Synthetic Peptides

Cell Chemical Biology
Yi KuangHirohide Saito

Abstract

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.

Citations

Dec 7, 2017·Chemical Communications : Chem Comm·Hongjian HeBing Xu
Mar 25, 2019·Angewandte Chemie·Huaimin WangBing Xu
Aug 14, 2020·Experimental & Molecular Medicine·Shoichiro TaniHironori Hojo
Apr 9, 2020·International Journal of Molecular Sciences·Alexandra LipusNico Lachmann
May 23, 2018·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Wai Long TamScott J Roberts
Nov 10, 2017·Nihon yakurigaku zasshi. Folia pharmacologica Japonica·Sho TanosakiKeiichi Fukuda
Jan 16, 2020·Inflammation and Regeneration·Yoshikazu KishinoKeiichi Fukuda
Aug 20, 2020·Chemical Reviews·Hongjian HeBing Xu
Jul 29, 2021·Biomaterials Science·Ning LiuZhanwei Zhou

❮ Previous
Next ❯

Related Concepts

Related Feeds

Allogenic & Autologous Therapies

Allogenic therapies are generated in large batches from unrelated donor tissues such as bone marrow. In contrast, autologous therapies are manufactures as a single lot from the patient being treated. Here is the latest research on allogenic and autologous therapies.