Modulated differentiation of embryonic stem cells into hepatocyte-like cells by coculture with hepatic stellate cells(CELL AND TISSUE ENGINEERING)
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概要
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We investigated the effects of coculture with hepatic stellate cells (HSCs) on the differentiation of embryonic stem (ES) cells and embryoid bodies (EBs). Rat HSCs were incubated until becoming semi-confluent and adherent to the dish. Undifferentiated mouse ES cells and 4-day EBs were cultured in gelatin-coated or HSC-feeder dishes, then induced hepatocyte-like cells and the remaining undifferentiated ES cells were examined using immunocytochemical and RT-PCR methods. HSCs promoted the differentiation of EBs into hepatocyte-like cells, whereas they inhibited the differentiation of undifferentiated ES cells. Among EB outgrowths cocultured with HSCs, albumin-immunopositive cells were clearly and abundantly observed, while they were faintly and scarcely seen in EB outgrowths without HSCs. mRNA expressions of the hepatocyte-related markers such as albumin, transthyretin, alpha-1-antitrypsin, tryptophan-2,3-dioxygenase, phosphoenolpyruvate carboxykinase, hepatocyte nuclear factor 4α and cytochrome P4507al were clearly detected in EB outgrowths cocultured with HSCs, while they were only weakly detected or undetected in spontaneous EB outgrowths without HSCs. In contrast to the promoted hepatic differentiation of EBs by HSCs, undifferentiated ES cells formed cellular colonies in HSC-feeder dishes that were similar to the colonies of undifferentiated ES cells kept in maintenance medium containing leukemia inhibitory factor. In addition, ES cell colonies were immunopositive for Oct-3/4, markers of an undifferentiated state, and there were few ALB-immunopositive cells in the colonies. Thus, HSCs have contrasting effects on EBs undergoing differentiation and undifferentiated ES cells, i.e., positive and negative modulation, respectively.
著者
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吉川 雅之
京都薬科大学
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吉川 雅之
Kyoto Pharmaceutical Univ.
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Nishimura Fumihiko
Program In Tissue Engineering Department Of Parasitology Nara Medical University
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Yoshikawa M
Program In Tissue Engineering Department Of Parasitology Nara Medical University
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Ouji Yukiteru
Program In Tissue Engineering Department Of Parasitology Nara Medical University
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Ouji Yukiteru
Department Of Chemical Engineering And Materials Science Faculty Of Engineering Doshisha University
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YAMADA Shuichi
Department of Neurosurgery, Nara Medical University
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NISHIMURA Fumihiko
Department of Neurosurgery, Nara Medical University
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FUKUI HIROSHI
Department of Biopharmaceutics, Kyoto Pharmaceutical University
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Moriya Kei
Program In Tissue Engineering Department Of Parasitology Nara Medical University
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Moriya Kei
Department Of Applied Biology Faculty Of Textile Science And Technology Shinshu University
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Fukui H
Department Of Internal Medicine Nara Medical University
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Fukui H
Kagawa Univ. Kagawa Jpn
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Morimoto Yukari
Third Department Of Internal Medicine Nara Medical University
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吉川 雅之
大阪大学薬学部
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YOSHIKAWA Masahide
Department of Parasitology, Nara Medical University
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NISHIOFUKU Mariko
Department of Hepato-Gastroenterology, Nara Medical University
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ISHIZAKA Shigeaki
Department of Parasitology, Nara Medical University
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Matsuda Ryosuke
Department of Neurosurgery, Nara Medical University
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Saito Ko
Department of Gastroenterology and Hepatology, Nara Medical University
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Yamada Shuichi
Department Of Neurosurgery Nara Medical University
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Matsuda Ryosuke
Program In Tissue Engineering Department Of Parasitology Nara Medical University
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Ishizaka Shigeaki
Program In Tissue Engineering Department Of Parasitology Nara Medical University
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Ishizaka Shigeaki
Department Of Parasitology Nara Medical University
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Yoshikawa Masaharu
First Department Of Internal Medicine Chiba University School Of Medicine
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Saito Ko
Department Of Gastroenterology And Hepatology Nara Medical University
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Saito Ko
Department Of Chemistry Graduate School Of Science Hiroshima University
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Masui Kazuhiro
Third Department Of Internal Medicine Nara Medical University
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Iwasawa Shu
Department Of Internal Medicine Takanohara General Hospital
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Matsuda Ryosuke
Department Of Neurosurgery Nara Medical University
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Yamazaki Masaharu
Department Of Internal Medicine Nara Medical University
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Nishimura Fumihiko
Department Of Neurosurgery Nara Medical University
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Nishiofuku Mariko
Department Of Parasitology Nara Medical University:department Of Gastroenterology And Hepatology Nar
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Fukui Hiroshi
Department Of Applied Biological Science Faculty Of Agriculture Kagawa University
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Fukui Hiroshi
Department Of Fermentation Technology Faculty Of Engineering Hiroshima University
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Fuku Hiroshi
The Third Department Of Internal Medicine Nara Medical University
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Yoshikawa Masahide
Department Of Internal Medicine Nara Medical University
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Yoshikawa Masahide
Department Of Gastroenterology Ishinkai Yao General Hospital
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Yamada Shuichi
Department of Applied Chemistry, Faculty of Technology, Kanagawa University
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Nishiofuku Mariko
Department of Gastroenterology, Ishinkai Yao General Hospital
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