Ammonia-based enrichment and long-term propagation of zone I hepatocyte-like cells
Abstract Ammonia has a cytotoxic effect and can therefore be used as a selection agent for enrichment of zone I hepatocytes. However, it has not yet been determined whether ammonia-treated hepatocyte-like cells are able to proliferate in vitro. In this study, we employed an ammonia selection strateg...
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2021
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oai:doaj.org-article:4f38116df54040ec862438c4cefb639a2021-12-02T17:50:41ZAmmonia-based enrichment and long-term propagation of zone I hepatocyte-like cells10.1038/s41598-021-90708-32045-2322https://doaj.org/article/4f38116df54040ec862438c4cefb639a2021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-90708-3https://doaj.org/toc/2045-2322Abstract Ammonia has a cytotoxic effect and can therefore be used as a selection agent for enrichment of zone I hepatocytes. However, it has not yet been determined whether ammonia-treated hepatocyte-like cells are able to proliferate in vitro. In this study, we employed an ammonia selection strategy to purify hepatocyte-like cells that were differentiated from human embryonic stem cells (ESCs) and from induced pluripotent stem cells (iPSCs). The resistance to cytotoxicity or cell death by ammonia is likely attributable to the metabolism of ammonia in the cells. In addition to ammonia metabolism-related genes, ammonia-selected hepatocytes showed increased expression of the cytochrome P450 genes. Additionally, the ammonia-selected cells achieved immortality or at least an equivalent life span to human pluripotent stem cells without affecting expression of the liver-associated genes. Ammonia treatment in combination with in vitro propagation is useful for obtaining large quantities of hepatocytes.Ruri TsuneishiNoriaki SakuShoko MiyataSaeko AkiyamaPalaksha Kanive JavaregowdaKenta IteNagisa TakashimaMasashi ToyodaTohru KimuraMasahiko KurodaAtsuko NakazawaMureo KasaharaHidenori NonakaAkihide KamiyaTohru KiyonoJunji YamauchiAkihiro UmezawaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021) |
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Medicine R Science Q Ruri Tsuneishi Noriaki Saku Shoko Miyata Saeko Akiyama Palaksha Kanive Javaregowda Kenta Ite Nagisa Takashima Masashi Toyoda Tohru Kimura Masahiko Kuroda Atsuko Nakazawa Mureo Kasahara Hidenori Nonaka Akihide Kamiya Tohru Kiyono Junji Yamauchi Akihiro Umezawa Ammonia-based enrichment and long-term propagation of zone I hepatocyte-like cells |
| description |
Abstract Ammonia has a cytotoxic effect and can therefore be used as a selection agent for enrichment of zone I hepatocytes. However, it has not yet been determined whether ammonia-treated hepatocyte-like cells are able to proliferate in vitro. In this study, we employed an ammonia selection strategy to purify hepatocyte-like cells that were differentiated from human embryonic stem cells (ESCs) and from induced pluripotent stem cells (iPSCs). The resistance to cytotoxicity or cell death by ammonia is likely attributable to the metabolism of ammonia in the cells. In addition to ammonia metabolism-related genes, ammonia-selected hepatocytes showed increased expression of the cytochrome P450 genes. Additionally, the ammonia-selected cells achieved immortality or at least an equivalent life span to human pluripotent stem cells without affecting expression of the liver-associated genes. Ammonia treatment in combination with in vitro propagation is useful for obtaining large quantities of hepatocytes. |
| format |
article |
| author |
Ruri Tsuneishi Noriaki Saku Shoko Miyata Saeko Akiyama Palaksha Kanive Javaregowda Kenta Ite Nagisa Takashima Masashi Toyoda Tohru Kimura Masahiko Kuroda Atsuko Nakazawa Mureo Kasahara Hidenori Nonaka Akihide Kamiya Tohru Kiyono Junji Yamauchi Akihiro Umezawa |
| author_facet |
Ruri Tsuneishi Noriaki Saku Shoko Miyata Saeko Akiyama Palaksha Kanive Javaregowda Kenta Ite Nagisa Takashima Masashi Toyoda Tohru Kimura Masahiko Kuroda Atsuko Nakazawa Mureo Kasahara Hidenori Nonaka Akihide Kamiya Tohru Kiyono Junji Yamauchi Akihiro Umezawa |
| author_sort |
Ruri Tsuneishi |
| title |
Ammonia-based enrichment and long-term propagation of zone I hepatocyte-like cells |
| title_short |
Ammonia-based enrichment and long-term propagation of zone I hepatocyte-like cells |
| title_full |
Ammonia-based enrichment and long-term propagation of zone I hepatocyte-like cells |
| title_fullStr |
Ammonia-based enrichment and long-term propagation of zone I hepatocyte-like cells |
| title_full_unstemmed |
Ammonia-based enrichment and long-term propagation of zone I hepatocyte-like cells |
| title_sort |
ammonia-based enrichment and long-term propagation of zone i hepatocyte-like cells |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/4f38116df54040ec862438c4cefb639a |
| work_keys_str_mv |
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