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US 2025/0164464 A1Published application
Liver organoid-derived cultured hepatocytes
AssigneeOsaka University
InventorsHiroyuki MIZUGUCHI, Yukiko UEYAMA TOBA, Jumpei INUI
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AssigneeOsaka University
InventorsHiroyuki MIZUGUCHI, Yukiko UEYAMA TOBA, Jumpei INUI
Estimating the term…
Provided is a high-function hepatic organoid-derived cultured hepatocyte, the hepatocyte being applicable to the evaluation of pharmacokinetics or the like in drug discovery research or the like. Also provided is a method of culturing a hepatic organoid for the production of the high-function hepatocyte. Also provided is a high-function pluripotent stem cell-derived hepatic organoid or a method of producing the pluripotent stem cell-derived hepatic organoid. A high-function cultured hepatocyte in which the gene expression level of a drug-metabolizing enzyme is high can be produced by a method including a step of detaching a hepatic organoid from a substrate for an organoid to separate the organoid into a single cell, followed by its two-dimensional culture or spheroid culture. The hepatic organoid-derived cultured hepatocyte of the present invention maintains not only the gene expression of the drug-metabolizing enzyme but also high drug-metabolizing enzyme activity, and hence can be effectively utilized in an in vitro pharmacokinetics evaluation. In particular, the cultured hepatocyte does not use a substrate that has been required for the holding of a three-dimensional structure in a hepatic organoid, and hence the cultured hepatocyte can effectively evaluate the toxicity of a drug without capture of various test compounds in a substrate such as Matrigel.
A cultured hepatocyte, comprising a hepatic organoid-derived cell, wherein a gene expression level of a drug-metabolizing enzyme of the cultured hepatocyte is increased as compared to a gene expression level of the drug-metabolizing enzyme of a hepatic organoid.
A method of producing a cultured hepatocyte including a hepatic organoid- derived cell, the method comprising the following steps:
A method of producing a cultured hepatocyte including a hepatic organoid- derived cell, the method comprising the following steps:
A medium for culturing a cultured hepatocyte including a hepatic organoid-derived cell, comprising:
A method of producing a pluripotent stem cell-derived hepatic organoid, comprising a step of producing the pluripotent stem cell-derived hepatic organoid from a cell obtained by culturing a pluripotent stem cell for at least 14 days.
A method of producing a pluripotent stem cell-derived hepatic organoid, comprising a step of producing the pluripotent stem cell-derived hepatic organoid from an iPS-derived hepatocyte.
A pluripotent stem cell-derived hepatic organoid, the pluripotent stem cell-derived hepatic organoid being intended for use in two-dimensional culture or spheroid culture.
Dependencies are inferred from the claim text.