A selective cytotoxic adenovirus vector for concentration of pluripotent stem cells in human pluripotent stem cell-derived neural progenitor cells

Abstract Highly sensitive detection of residual undifferentiated pluripotent stem cells is essential for the quality and safety of cell-processed therapeutic products derived from human induced pluripotent stem cells (hiPSCs). We previously reported the generation of an adenovirus (Ad) vector and ad...

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Autores principales:	Takamasa Hirai, Ken Kono, Rumi Sawada, Takuya Kuroda, Satoshi Yasuda, Satoko Matsuyama, Akifumi Matsuyama, Naoya Koizumi, Naoki Utoguchi, Hiroyuki Mizuguchi, Yoji Sato
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2735b6808bb54562a53b506bb3e6702e
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spelling	oai:doaj.org-article:2735b6808bb54562a53b506bb3e6702e2021-12-02T17:51:13ZA selective cytotoxic adenovirus vector for concentration of pluripotent stem cells in human pluripotent stem cell-derived neural progenitor cells10.1038/s41598-021-90928-72045-2322https://doaj.org/article/2735b6808bb54562a53b506bb3e6702e2021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-90928-7https://doaj.org/toc/2045-2322Abstract Highly sensitive detection of residual undifferentiated pluripotent stem cells is essential for the quality and safety of cell-processed therapeutic products derived from human induced pluripotent stem cells (hiPSCs). We previously reported the generation of an adenovirus (Ad) vector and adeno-associated virus vectors that possess a suicide gene, inducible Caspase 9 (iCasp9), which makes it possible to sensitively detect undifferentiated hiPSCs in cultures of hiPSC-derived cardiomyocytes. In this study, we investigated whether these vectors also allow for detection of undifferentiated hiPSCs in preparations of hiPSC-derived neural progenitor cells (hiPSC-NPCs), which have been expected to treat neurological disorders. To detect undifferentiated hiPSCs, the expression of pluripotent stem cell markers was determined by immunostaining and flow cytometry. Using immortalized NPCs as a model, the Ad vector was identified to be the most efficient among the vectors tested in detecting undifferentiated hiPSCs. Moreover, we found that the Ad vector killed most hiPSC-NPCs in an iCasp9-dependent manner, enabling flow cytometry to detect undifferentiated hiPSCs intermingled at a lower concentration (0.002%) than reported previously (0.1%). These data indicate that the Ad vector selectively eliminates hiPSC-NPCs, thus allowing for sensitive detection of hiPSCs. This cytotoxic viral vector could contribute to ensuring the quality and safety of hiPSCs-NPCs for therapeutic use.Takamasa HiraiKen KonoRumi SawadaTakuya KurodaSatoshi YasudaSatoko MatsuyamaAkifumi MatsuyamaNaoya KoizumiNaoki UtoguchiHiroyuki MizuguchiYoji SatoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Takamasa Hirai Ken Kono Rumi Sawada Takuya Kuroda Satoshi Yasuda Satoko Matsuyama Akifumi Matsuyama Naoya Koizumi Naoki Utoguchi Hiroyuki Mizuguchi Yoji Sato A selective cytotoxic adenovirus vector for concentration of pluripotent stem cells in human pluripotent stem cell-derived neural progenitor cells
description	Abstract Highly sensitive detection of residual undifferentiated pluripotent stem cells is essential for the quality and safety of cell-processed therapeutic products derived from human induced pluripotent stem cells (hiPSCs). We previously reported the generation of an adenovirus (Ad) vector and adeno-associated virus vectors that possess a suicide gene, inducible Caspase 9 (iCasp9), which makes it possible to sensitively detect undifferentiated hiPSCs in cultures of hiPSC-derived cardiomyocytes. In this study, we investigated whether these vectors also allow for detection of undifferentiated hiPSCs in preparations of hiPSC-derived neural progenitor cells (hiPSC-NPCs), which have been expected to treat neurological disorders. To detect undifferentiated hiPSCs, the expression of pluripotent stem cell markers was determined by immunostaining and flow cytometry. Using immortalized NPCs as a model, the Ad vector was identified to be the most efficient among the vectors tested in detecting undifferentiated hiPSCs. Moreover, we found that the Ad vector killed most hiPSC-NPCs in an iCasp9-dependent manner, enabling flow cytometry to detect undifferentiated hiPSCs intermingled at a lower concentration (0.002%) than reported previously (0.1%). These data indicate that the Ad vector selectively eliminates hiPSC-NPCs, thus allowing for sensitive detection of hiPSCs. This cytotoxic viral vector could contribute to ensuring the quality and safety of hiPSCs-NPCs for therapeutic use.
format	article
author	Takamasa Hirai Ken Kono Rumi Sawada Takuya Kuroda Satoshi Yasuda Satoko Matsuyama Akifumi Matsuyama Naoya Koizumi Naoki Utoguchi Hiroyuki Mizuguchi Yoji Sato
author_facet	Takamasa Hirai Ken Kono Rumi Sawada Takuya Kuroda Satoshi Yasuda Satoko Matsuyama Akifumi Matsuyama Naoya Koizumi Naoki Utoguchi Hiroyuki Mizuguchi Yoji Sato
author_sort	Takamasa Hirai
title	A selective cytotoxic adenovirus vector for concentration of pluripotent stem cells in human pluripotent stem cell-derived neural progenitor cells
title_short	A selective cytotoxic adenovirus vector for concentration of pluripotent stem cells in human pluripotent stem cell-derived neural progenitor cells
title_full	A selective cytotoxic adenovirus vector for concentration of pluripotent stem cells in human pluripotent stem cell-derived neural progenitor cells
title_fullStr	A selective cytotoxic adenovirus vector for concentration of pluripotent stem cells in human pluripotent stem cell-derived neural progenitor cells
title_full_unstemmed	A selective cytotoxic adenovirus vector for concentration of pluripotent stem cells in human pluripotent stem cell-derived neural progenitor cells
title_sort	selective cytotoxic adenovirus vector for concentration of pluripotent stem cells in human pluripotent stem cell-derived neural progenitor cells
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/2735b6808bb54562a53b506bb3e6702e
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A selective cytotoxic adenovirus vector for concentration of pluripotent stem cells in human pluripotent stem cell-derived neural progenitor cells

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