The present invention pertains to hepatocytes, liver progenitor cells, cholangiocytes, liver sinusoidal endothelial progenitor cells, liver sinusoidal endothelial cells, hepatic stellate progenitor cells, hepatic stellate cells, and liver cellular tissue models, as well as to methods for preparing these cells. The present invention also pertains to a cell fraction comprising liver progenitor cells, liver sinusoidal endothelial progenitor cells, or hepatic stellate progenitor cells. The present invention also pertains to a pharmaceutical composition or kit comprising the above-mentioned cells, a liver cellular tissue model, or a cell fraction. The present invention also pertains to: a method for screening liver disease treatment agents; a method for evaluating the hepatotoxicity of drugs, hepatocytes for infectious disease models, and a method for preparing the same; infectious disease model tissues and a method for preparing the same; as well as a method for screening infectious liver disease treatment agents.

This application describes liver stem cells (LSC), and differentiated hepatocytes, cholangiocytes, and 3D cellular structures derived therefrom. Methods for producing LSC and mature, differentiated hepatocytes and cholangiocytes in culture are provided. Also provided are cell culture systems and cell culture media for producing a homogenous population of liver stem cells that remain in an undifferentiated state over multiple passages in culture. The LSC and methods are useful for producing homogenous populations of hepatocytes and cholangiocytes for downstream applications. The LSC can be transplanted into subjects to treat liver diseases.

Disclosed are methods of treating or reducing the occurrence of a steatohepatitis disorder. The disorder may include, for example, NASH, parenteral nutrition associated liver disease (PNALD), or genetic forms of liver disease. The method may comprise the step of administering a composition comprising obeticholic acid to an individual in need thereof.

The present invention relates to a human adult hepatocyte reprogramming medium composition and provides a method for inducing hepatic progenitor cells from human adult hepatocytes by means of a combination of chemicals.

The present invention relates material that is useful in culturing and transferring cells as well as delivering cells. The material comprises plant derived cellulose nanofibers or derivatives thereof, wherein the cellulose nanofibers are in a form of a hydrogel or membrane. The invention also provides methods for producing these materials and compositions and uses thereof.

Novel adult liver progenitor cells (called H2Stem Cells) have been have been characterized on the basis of a series of biological activities and markers. Methods for producing H2Stem Cells allow providing such cells in the form of adherent cells and three-dimensional cell clusters in suspension that can be differentiated into cells having strong liver-specific activities and/or that can be used for treating liver diseases or for evaluating the efficacy, the metabolism, and/or toxicity of a compound.

An object of the present invention is to provide an artificial liver using highly functional hepatocytes. There is provided an extracorporeal artificial liver having at least one module comprising the followings: a plasma ingredient inlet port, and a plasma ingredient outlet port; a plasma ingredient circulation chamber having the plasma ingredient inlet port, and the plasma ingredient outlet port; and a hepatocyte culture chamber provided adjacently to the plasma ingredient circulation chamber and separated from the plasma ingredient circulation chamber with a separation membrane through which ammonia can permeate, but hepatocytes cannot permeate, in which hepatocytes having an ammonia-metabolizing ability are cultured.

Disclosed herein are methods of making and using lipotoxic organoid models. In certain aspects, the methods may comprise the steps of contacting a liver organoid with a free fatty acid (FFA) composition. In one aspect, the FFA composition may comprise oleic acid, linoleic acid, palmitic acid, or combinations thereof.

Novel adult liver progenitor cells (called H2Stem Cells) have been have been characterized on the basis of a series of biological activities and markers. Methods for producing H2Stem Cells allow providing such cells in the form of adherent cells and three-dimensional cell clusters in suspension that can be differentiated into cells having strong liver-specific activities and/or that can be used for treating liver diseases or for evaluating the efficacy, the metabolism, and/or toxicity of a compound.

Provided are: a method for producing biliary epithelial progenitor cells, said method comprising a step for culturing hepatoblasts in a medium containing TGF and EGF; and a method for constructing a three-dimensional duct-like structure of biliary epithelial progenitor cells, said method comprising a step for culturing hepatoblasts or biliary epithelial progenitor cells in a medium containing HGF, EGF, a Notch inhibitor and a GSK3 inhibitor in the presence of a three-dimensional scaffold material.