The invention relates to the use of a laminin (LN) as a matrix for hepatic differentiation. The invention also relates to a method for inducing hepatic differentiation comprising the steps of: (i) providing a population of human pluripotent cells, (ii) culturing the population on a support coated with a laminin in a endoderm induction medium to produce a population of human DE cells, (iii) culturing said population of human DE cells on a support coated with a laminin in a hepatic induction medium to produce a population of human hepatoblasts-like cells, and (iv) optionally culturing said population of human hepatoblasts-like cells on a support coated with a laminin in a hepatic maturation medium to produce a population of human hepatocyte-like cells. The invention further relates to a population of human hepatoblasts-like cells or human fetal hepatocyte-like cells obtained by the method of the invention. The invention further relates to a population of human hepatoblasts-like cells expressing HNF4 ? and expressing substantially AFP for use in a method of treatment of the human body.

The invention described herein relates to methods of isolating non-embryonic stem cell, e.g., adult stem cell, from a non-embryonic tissue, e.g., an adult tissue or organ. Non-embryonic stem cells (e.g., adult stem cells) thus isolated from the various tissues or organs can self-renew or propagate indefinitely in vitro, are multipotent and can differentiate into the various differentiated cell types normally found within the tissue or organ from which the stem cells are isolated. In addition, the isolated stem cells can be propagated through clonal expansion of a single isolated stem cell, to produce a clone of which at least about 40%, 70%, or 90% or more cells within the clone can be further passaged as single cell originated clones.

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.

The present invention relates to a method for preparing induced hepatic progenitor cells (iHPC) comprising the steps of dedifferentiation of hepatocytes by culture with a culture medium comprising at least one activator of the Wnt signaling, Basic fibroblast growth factor (b-FGF), and Epidermal growth factor (EGF).

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.

Methods and systems are provided for a stem cell organ device including an array of alternating stem cell channels and fluid channels. In one example, a method may include loading a stem cell channel with stem cells and flowing blood through a fluid channel in order to allow an exchange of molecules between the stem cells and the blood.

Methods are provided for producing differentiated cells from stem cells, including producing hepatocytes. Compositions thereof are also provided, as are methods of treating a liver disorder.

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 is to provide a method of differentiating pluripotent stem cells. A method of differentiating pluripotent stem cells, the method comprising steps of: seeding the pluripotent stem cells in a container provided with seeding medium! differentiating the pluripotent stem cells in the container; transferring the pluripotent stem cells from the container into a chamber of a bioreactor when the pluripotent stem cells reach their progenitor stage; and maturing the pluripotent stem cells in the chamber, wherein a floor of the chamber includes a concave and a convex, fluid of medium flows in the chamber and oxygen is supplied into the chamber.

Subpopulations of spore-like cells expressing specific cell surface and gene expression markers are provided. In one embodiment, the cells express at least one cell surface or gene expression marker selected from the group consisting of Oct4, nanog, Zfp296, cripto, Gdf3, UtF1, Ecat1, Esg1, Sox2, Pax6, nestin, SCA-1, CD29, CD34, CD90, B1 integrin, cKit, SP-C, CC10, SF1, DAX1, and SCG10. Also provided are methods for purifying a subpopulation of spore-like cells of interest from a population of spore-like cells, and methods for inducing differentiation of the isolated spore-like cells into cells of endodermal, mesodermal or ectodermal origin. The spore-like cells can be used to generate cells originating from all three germ layers and can be used to treat a patient who has a deficiency of functional cells in any of a wide variety of tissues, including the retina, intestine, bladder, kidney, liver, lung, nervous system, or endocrine system.