The present disclosure relates to a non-alcoholic fatty liver artificial tissue model. As compared to a conventional technology by which tissues are cultured only in Matrigel including a device composed of a decellularized liver tissue-derived extracellular matrix and a plurality of microchannels or a decellularized liver tissue-derived extracellular matrix, the present disclosure enables better mimicking of an actual non-alcoholic fatty liver disease due to the presence of Kupffer cells and hepatic stellate cells. Also, according to the present disclosure, the growth of liver organoids can be improved and fat accumulation and inflammation in the liver organoids can be caused to occur well through free fatty acid treatment, and the phenotypes of non-alcoholic fatty liver can be better expressed.

Preparations of adult liver progenitor cells (called HHALPCs) have been manufactured from different human donors and characterized by using cell surface markers that allow identifying HHALPCs preparations and/or the methods for producing them that are most suitable for cell therapy, in particular for treating liver diseases or inherited blood coagulation disorders.

The present invention relates to nanoparticles for the targeted delivery of antigen to liver cells, in particular, liver sinusoidal endothelial cells (LSEC) and/or Kupffer cells, and for the in vivo generation of regulatory T cells, notably CD4+CD25+FOXP3+ regulatory T cells (Treg). The invention provides pharmaceutical compositions and methods for the prevention and treatment of autoimmune diseases, allergies or other chronic inflammatory conditions, and for generation of regulatory T cells. The nanoparticles used in the invention comprise a) a micelle comprising an amphiphilic polymer rendering the nanoparticle water-soluble, and b) a peptide comprising at least one T cell epitope associated with the outside of the micelle. The micelle may or may not comprise a solid hydrophobic core.

Provided is a selective method for inducing differentiation from pluripotent stem cells to enterocyte-like cells. Also provided is an excellent enterocyte-like cell expressing drug-metabolizing enzymes and drug transporters. More specifically, provided is an enterocyte-like cell having properties closer to those of primary enterocytes, which are difficult to acquire. The foregoing is achieved by adding an ALK5 inhibitor (SB431542), Wnt3a, and EGF to a culture system of definitive endoderm cells obtained by differentiation induction from pluripotent stem cells and extending a culture time. The foregoing is also achieved by introducing CDX2 gene and/or FOXA2 gene into the pluripotent stem cells or the definitive endoderm cells. The foregoing is also achieved by overlaying a basement membrane matrix on the enterocyte-like cells.

Provided herein are cell compositions useful for making artificial liver constructs. The cell composition my include, in combination, (a) hepatocyte cells, (b) Kuppfer cells, (c) hepatic stellate cells, (d) sinusoidal endothelial cells, and (e) cholangiocyte cells.

The invention relates to cell-free compositions obtained by culturing adult-derived human liver stem/progenitor cells (ADHLSC) in cell culture medium and isolating the resulting conditioned medium (ADHLSC-CM) that has advantageous properties, such as anti-fibrotic effects. ADHLSC-CM, compositions based on ADHLSC-CM, and other related and derived products, can be used in cell culture processes or as a medicament, more particularly for the treatment of diseases involving organ injury, organ failure, in organ or cell transplantation or the pathological disruption, inflammation, degeneration, and/or proliferation of cells within a tissue or an organ, in particular within liver.

A method of making a cardiac construct is carried out by depositing a mixture comprising live mammalian cardiac cells (e.g., individual cells, organoids, or spheroids), fibrinogen, gelatin, and water on a support to form an intermediate cardiac construct; optionally co-depositing a structural support material (e.g., polycaprolactone) with the mixture in a configuration that supports the intermediate construct; and then contacting thrombin to the construct in an amount effective to cross-link the fibrinogen and produce a cardiac construct comprised of live cardiac cells that together spontaneously beat in a fibrin hydrogel. Constructs made and methods of using the same are also described.

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.

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.

Methods for producing hepatocyte and/or cholangiocyte lineage cells from pluripotent stem cells, the method comprising (a) specifying the extended nodal agonist treated induced endodermal cell population to obtain a cell population comprising hepatocyte and/or cholangiocyte progenitors by contacting the extended nodal agonist treated induced endodermal cell population with specification media comprising a FGF agonist and a BMP4 agonist and/or active conjugates and/or fragments thereof; (b) inducing maturation, and optionally further lineage specification and/or expansion of the hepatocyte and/or cholangiocyte progenitors of the cell population to obtain a population comprising hepatocyte lineage cells such as hepatoblasts, hepatocytes and/or cholangiocytes, the inducing maturation step comprising generating aggregates of the cell population. Optionally, the method also comprises activating the cAMP pathway within the aggregates and forming co-aggregates.