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.

The present invention relates to a composition for inducing direct conversion from a somatic cell into one or more kinds selected from the group consisting of an induced Hepatic stem cell (iHSC), a hepatocyte, and a cholangiocyte, and a method of direct conversion of a somatic cell into one or more kinds selected from the group consisting of an induced Hepatic stem cell, a hepatocyte, and a cholangiocyte.

The current invention concerns liver progenitor or stem cells, lysates thereof, and/or conditioned medium obtainable by culturing liver progenitor or stem cells in said medium for use in the treatment of diseases and/or conditions caused by increased vascular permeability or for use in restoring the vascular integrity of cells and tissues in a subject following inflammation and/or infection in said subject. More particularly, the present invention relates to liver progenitor or stem cells or conditioned medium obtainable by culturing liver progenitor or stem cells in said medium for therapeutic use in sepsis and sepsis-induced diseases, such as myocardial edema, acute kidney injury and lung sepsis.

The present invention provides a means for suppressing formation and/or proliferation of undesired cells derived from stem cells in a cell population containing cells differentiated from stem cells. The nutrition composition according to the present invention is a nutrition composition for suppressing formation and/or proliferation of undesired cells derived from stem cells in a cell population containing cells differentiated from stem cells, the nutrition composition containing at least one essential amino acid selected from the group consisting of isoleucine, leucine, methionine, lysine, phenylalanine, tryptophan, threonine and histidine except valine, and optionally containing a non-essential amino acid(s).

A cultured tissue, comprising: glandular cells; glandular cavities formed from the glandular cells; and ducts formed from epithelial cells, wherein the glandular cavities and the ducts are functionally connected ex vivo.

The present invention relates to a process for producing liver cells, especially liver stem cells, which after injection into a mammal or in vitro form liver cells that are differentiated, especially differentiated into hepatocytes, into cholangiocytes, and preferably also into liver sinusoidal endothelial cells (LSEC) that can e.g. form blood sinusoidal capillaries. The invention is based on in in vitro producing liver stem cells from a sample of liver tissue, cultivating the liver stem cells in vitro for an increase in cell number. It has been found that the liver stem cells that are produced by the process of the invention can be cultivated and increased in number while maintaining their capability to differentiate into liver cells, especially into hepatocytes, cholangiocytes, and preferably also into LSEC. Accordingly, the process of the invention is suitable for producing liver stem cells that are autologous for the originator of the sample of liver tissue.

A method for inducing non-hepatocytes into hepatocyte-like cells, wherein the non-hepatocytes are induced to express or overexpress hepatic fate conversion and maturation factors, cultured in somatic cell culture medium, hepatocyte expansion culture medium and 2C medium for a sufficient period of time to convert the non-hepatocyte cell into cells with hepatocyte-like properties, are provided. The iHeps induced according to the methods are also provided.

The present invention relates to a method for producing a cell having a genetic defect corrected, and a cell therapy agent comprising the cell, and, more particularly, to a method for producing a cell and a cell therapy agent comprising the cell, which comprise a method for isolating a cell from an individual, producing a chemically derived progenitor cell by processing a compound, and then correcting a mutant gene ex vivo.

The cell therapy agent of the present invention has significantly less side effects such as an off-target effect and tumor generation, and has shown a Tyrosinemia type I treatment effect that is more significant than when a simple cell is transplanted, and thus, the cell therapy agent is expected to be widely usable in treatment fields for diseases caused by gene mutation, including Tyrosinemia type I.

Provided are a method for expanding a hepatocyte in vitro and an application thereof. A culture system is provided for reprogramming a human hepatocyte into a proliferating intermediate-state cell between a mature hepatocyte and a liver progenitor cell. The liver repopulation ability of the system was verified in animals. The method does not require the introduction of an exogenous gene into a hepatocyte, and the expansion of the hepatocyte can be realized by conventional culture. The obtained hepatocyte can be passaged, and can be cultured to maturation to obtain a functional mature human hepatocyte.

A pluripotent stem cell, a method for producing the pluripotent stem cell, and the use of the pluripotent stem cell for stem cell differentiation, cell transplantation, tissue repair, and/or tissue regeneration.