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PeerJ. 2018 Jan 4;6:e4187. doi: 10.7717/peerj.4187. eCollection 2018.

Small-scale screening of anticancer drugs acting specifically on neural stem/progenitor cells derived from human-induced pluripotent stem cells using a time-course cytotoxicity test.

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Division of Stem Cell Research, Institute for Clinical Research, Osaka National Hospital, National Hospital Organization, Osaka, Japan.
Division of Regenerative Medicine, Institute for Clinical Research, Osaka National Hospital, National Hospital Organization, Osaka, Japan.
Department of Neurosurgery, Osaka National Hospital, National Hospital Organization, Osaka, Japan.
Department of Physiology, Keio University School of Medicine, Tokyo, Japan.


Since the development of human-induced pluripotent stem cells (hiPSCs), various types of hiPSC-derived cells have been established for regenerative medicine and drug development. Neural stem/progenitor cells (NSPCs) derived from hiPSCs (hiPSC-NSPCs) have shown benefits for regenerative therapy of the central nervous system. However, owing to their intrinsic proliferative potential, therapies using transplanted hiPSC-NSPCs carry an inherent risk of undesired growth in vivo. Therefore, it is important to find cytotoxic drugs that can specifically target overproliferative transplanted hiPSC-NSPCs without damaging the intrinsic in vivo stem-cell system. Here, we examined the chemosensitivity of hiPSC-NSPCs and human neural tissue-derived NSPCs (hN-NSPCs) to the general anticancer drugs cisplatin, etoposide, mercaptopurine, and methotrexate. A time-course analysis of neurospheres in a microsphere array identified cisplatin and etoposide as fast-acting drugs, and mercaptopurine and methotrexate as slow-acting drugs. Notably, the slow-acting drugs were eventually cytotoxic to hiPSC-NSPCs but not to hN-NSPCs, a phenomenon not evident in the conventional endpoint assay on day 2 of treatment. Our results indicate that slow-acting drugs can distinguish hiPSC-NSPCs from hN-NSPCs and may provide an effective backup safety measure in stem-cell transplant therapies.


ATP assay; Anticancer drugs; Drug screening; Endpoint assay; Human fetal neural tissue; Human-induced pluripotent stem cells; Microsphere array; Neural stem/progenitor cells; Neurosphere; Time-course cytotoxicity test

Conflict of interest statement

The authors declare there are no competing interests.

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