Title:
METHOD FOR INDUCING HEPATOCYTE PLASTICITY
Document Type and Number:
WIPO Patent Application WO/2021/060380
Kind Code:
A1
Abstract:
Provided are: a method for inducing hepatic progenitor cells which can overcome drawbacks in the prior art; and hepatic progenitor cells. Hepatocyte plasticity and senescence are controlled. A method for producing hepatocytes that includes dividing endodermal cells into hepatocytes in the presence of a member of the FGF family, HGF, and a member of IL6 family, and dexamethazone. Hepatocytes produced using the aforementioned method that can survive for 90 or more days while maintaining functionality as hepatocytes. A method for producing hepatic progenitor cells that includes culturing hepatocytes in the presence of a member of the FGF family. Alpha-fetoprotein (AFP)–negative hepatic progenitor cells produced using the aforementioned method that have proliferative ability and the ability to differentiate bidirectionally into hepatocytes and bile duct epithelial cells. A method for producing hepatocytes that includes inducing differentiation of the hepatic progenitor cells into hepatocytes. A method for producing bile duct cells that includes inducing differentiation of the hepatic progenitor cells into bile duct cells. A method for suppressing hepatocyte senescence using a drug which causes histone hyperacetylation. A hepatocyte senescence inhibitor that includes a drug that causes histone hyperacetylation as an active ingredient. A method for increasing hepatocyte plasticity using a drug that causes histone hyperacetylation. A drug that increases hepatocyte plasticity and includes a drug that causes histone hyperacetylation as an active ingredient. A method for producing a chimeric animal that includes transplanting into a non-human animal at least one cell selected from the group consisting of the hepatocytes, the hepatic progenitor cells, and the cells induced through differentiation from the hepatic progenitor cells. A composition for transplantation that includes at least one cell selected from the group consisting of the hepatocytes, the hepatic progenitor cells, and the cells induced by differentiation from the hepatic progenitor cells. A culture medium kit for inducing differentiation that includes: an agent containing FGF10, retinoic acid, and forskolin for use in a culture medium to be used to induce differentiation of the hepatic progenitor cells into bile duct cells; and a written explanation of the use of the agent in the culture medium to be used to induce differentiation. A medium containing FGF10, retinoic acid, and forskolin for inducing differentiation of the hepatic progenitor cells into bile duct cells. A liver regeneration promoter that includes a drug that causes histone hyperacetylation as an active ingredient.
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Inventors:
TANIGUCHI HIDEKI (JP)
NIE YUNZHONG (JP)
ZHENG YUNWEN (JP)
NIE YUNZHONG (JP)
ZHENG YUNWEN (JP)
Application Number:
PCT/JP2020/036043
Publication Date:
April 01, 2021
Filing Date:
September 24, 2020
Export Citation:
Assignee:
PUBLIC UNIV CORP YOKOHAMA CITY UNIV (JP)
International Classes:
A61P1/16; A01K67/027; A61K31/573; A61K35/407; A61L27/38; A61P43/00; C12N5/071; C12N5/0735; C12N5/10; C12N15/09
Domestic Patent References:
| WO2017216342A1 | 2017-12-21 |
Foreign References:
| JP2018524980A | 2018-09-06 |
Other References:
BANAS, A. ET AL.: "Rapid hepatic fate specification of adipose-derived stem cells and their therapeutic potential for liver failure", JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, vol. 24, 2009, pages 70 - 77, XP055338968, DOI: 10.1111/j.1440-1746.2008.05496.x
VAN BEZOOIJEN, C. F. A. ET AL.: "Albumin synthesis by liver parenchymal cells isolated from young, adult and old rats", BIOCHEM. BIOPHYS. RES. COMMUN., vol. 71, no. 2, 1976, pages 513 - 519, XP024772003, DOI: 10.1016/0006-291X(76)90817-2
SAMPAZIOTIS, F. ET AL.: "Directed differentiation of human induced pluripotent stem cells into functional cholagiocyte-like cells", NAT. PROTOC., vol. 12, no. 4, 2017, pages 814 - 827, XP055534582, DOI: 10.1038/nprot.2017.011
NAKAMURA, NAOKO ET AL.: "Parameters of stem cell-derived functional hepatocytes", ORGAN BIOLOGY, vol. 21, no. 1, 10 April 2014 (2014-04-10), pages 33 - 41, XP055809401
SHIRAI, AYUMI ET AL.: "Analysis of hepatocyte characteristics and examination of hepatocyte differentiation potential of primary cultured cells derived from human egg membrane tissue, abstract CD", BIOCHEMIE, 2008
VAN BEZOOIJEN, C. F. A. ET AL.: "Albumin synthesis by liver parenchymal cells isolated from young, adult and old rats", BIOCHEM. BIOPHYS. RES. COMMUN., vol. 71, no. 2, 1976, pages 513 - 519, XP024772003, DOI: 10.1016/0006-291X(76)90817-2
SAMPAZIOTIS, F. ET AL.: "Directed differentiation of human induced pluripotent stem cells into functional cholagiocyte-like cells", NAT. PROTOC., vol. 12, no. 4, 2017, pages 814 - 827, XP055534582, DOI: 10.1038/nprot.2017.011
NAKAMURA, NAOKO ET AL.: "Parameters of stem cell-derived functional hepatocytes", ORGAN BIOLOGY, vol. 21, no. 1, 10 April 2014 (2014-04-10), pages 33 - 41, XP055809401
SHIRAI, AYUMI ET AL.: "Analysis of hepatocyte characteristics and examination of hepatocyte differentiation potential of primary cultured cells derived from human egg membrane tissue, abstract CD", BIOCHEMIE, 2008
Attorney, Agent or Firm:
MAYAMA, Setsuko et al. (JP)
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