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AssigneesDNAVEC Corporation, National Center for Global Health and Medicine
InventorsAkira Yuo, Kumiko Saeki, Naoko Nakamura, Satoko Matsuyama, Miwako Nishio, Koichi Saeki, Mamoru Hasegawa
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The problem is to produce functional liver cells usable in testing the metabolism and toxicity of a drug, from pluripotent stem cells. The solution includes a method for producing highly functional liver cells using pluripotent stem cells, comprising, from pluripotent stem cells, acquiring primitive endoderm derived from the pluripotent stem cells by a process involving steps (A) and (B), from the primitive endoderm, acquiring liver precursor cells by a process involving step (C), and, from the liver precursor cells, acquiring the highly functional liver cells by a process involving step (D): (A) culturing under serum-free and feeder-free conditions; (B) culturing in the presence of albumin and at least one kind of cytokine; (C) culturing in the presence of SHH or an SHH agonist and at least one kind of cytokine; and (D) culturing and maturing in the presence of at least one kind of cytokine.
A method for producing highly functional hepatocytes using pluripotent stem cells, comprising:
A method for producing pluripotent stem cell-derived primitive endoderms using pluripotent stem cells, comprising:
A method of producing liver progenitor cells using primitive endoderms, the method comprising:
A method for producing highly functional hepatocytes using liver progenitor cells, comprising:
A highly functional hepatocyte produced from a pluripotent stem cell, wherein the pluripotent stem cell-derived highly functional hepatocyte shows a cytochrome P450 enzymatic activity in the presence of dexamethasone at a level twice or more that of a HepaRG cell, has ICG uptake and release activities, is PAS staining positive, expresses A1AT, and is capable of differentiating into a bile duct epithelial cell.
Dependencies are inferred from the claim text.