The disclosure provides a method for producing hepatocytes or hepatic progenitor cells; a method for suppressing hepatocyte aging using a drug causing histone hyperacetylation; a hepatocyte anti-aging agent; a method for increasing hepatocyte plasticity; and a drug for increasing hepatocyte plasticity.

Provided herein are methods and compositions related to a method of stimulating the immune system in a subject in need thereof by administering an agent that increases the level or activity of indoleamine 2,3-dioxygenase (IDO1) and/or aryl hydrocarbon receptor (Ahr).

A method of making a live cell construct is carried out by: (a) providing a non-cellular support having a top surface and a bottom surface, (b) contacting live undifferentiated cells to the non-cellular support, and then (c) propagating a gastrointestinal epithelial cell monolayer on said top surface. In some embodiments, the live cells in the monolayer include: (i) undifferentiated cells (e.g., stem or progenitor cells); and (ii) optionally, but in some embodiments preferably, differentiated cells (e.g., enterocytes, Paneth cells, enteroendocrine cells, tuft cells, microcells, intra-epithelial lymphocytes, and/or goblet cells). Constructs formed by such methods and methods of using the same (e.g., in high through-put screening) are also described.

Provided are a primary cell culture medium that contains a combination of an MST1/2 kinase inhibitor and a ROCK kinase inhibitor and is used for culturing primary esophageal squamous cell carcinoma epithelial cells, and a culture method using the primay cell culture medium. In the culture method, the primary cell culture medium is used to culture primay cells on a culture vessel coated with an extracellular matrix glue, so that the primary cells prolilferate rapidly. A cell model obtained by using the primary cell culture medium and the primary cell culture method of the present invention can be used for the efficacy evaluation and screening of drugs.

An in vitro microfluidic intestine on-chip is described herein that mimics the structure and at least one function of specific areas of the gastrointestinal system in vivo. In particular, a multicellular, layered, microfluidic intestinal cell culture, which is some embodiments is derived from patient's enteroids-derived cells, is described comprising L cells, allowing for interactions between L cells and gastrointestinal epithelial cells, endothelial cells and immune cells. This in vitro microfluidic system can be used for modeling inflammatory gastrointestinal autoimmune tissue, e.g., diabetes, obesity, intestinal insufficiency and other inflammatory gastrointestinal disorders. These multicellular-layered microfluidic intestine on-chips further allow for comparisons between types of gastrointestinal tissues, e.g., small intestinal duodenum, small intestinal jejunum, small intestinal ileum, large intestinal colon, etc., and between disease states of gastrointestinal tissue, i.e. healthy, pre-disease and diseased areas. Additionally, these microfluidic gut-on-chips allow identification of cells and cellular derived factors driving disease states and drug testing for reducing inflammation.

Disclosed are compositions, in particular, organoid compositions, derived from more than one donor cell. Further disclosed are methods of making compositions, for example, organoid compositions, that comprise a differentiated cell population derived from more than one donor cell. Donor cells may include, for example, a precursor cell such as an embryonic stem cell or other precursor cell. The disclosed methods use synchronization conditions to produce a synchronized pooled-precursor cell population, which may then be differentiated into an organoid composition. Methods of using the compositions are also disclosed.

An antibody is provided that inhibits infection of cells with a norovirus. The antibody is a nanoantibody comprising a polypeptide described in (a), (b), or (c), and inhibiting infection of intestinal cells with HuNoV GII.4: (a) a polypeptide consisting of the amino acid sequence of SEQ ID NO: 1, SEQ ID NO: 5, SEQ ID NO: 9, or SEQ ID NO: 13; (b) a polypeptide consisting of an amino acid sequence comprising a substitution, deletion, insertion and/or addition of one or several amino acids with respect to the amino acid sequence of SEQ ID NO: 1, SEQ ID NO: 5, SEQ ID NO: 9, or SEQ ID NO: 13; and (c) a polypeptide consisting of an amino acid sequence having a sequence identity of 80% or more to the amino acid sequence of SEQ ID NO: 1, SEQ ID NO: 5, SEQ ID NO: 9, or SEQ ID NO: 13.

There is provided an in vitro three dimensional cell construct for use as a model of the avian intestine derived from avian intestinal tissue comprising avian cells organised into intestinal villi and crypts. Suitably the construct comprises an exterior surface that mimics the apical surface of a chicken intestine. Also provided are methods of making the cell construct and use of the construct as an in vitro intestinal model system to examine an agent including, but not limited to a microbe, a vaccine, a pharmaceutical, a feed additive, a toxin, a pre-biotic, post-biotic, pre pro post biotic, therapeutic, a cell, gene construct, protein, immune-modulator, an intestinal effector agent, a candidate intestinal effector agent, cell signalling inhibitor, or cell signalling activator.

The invention concerns novel methods and materials for preparing extracellular matrix (ECM) powder pre-gel and gel solutions, for example for use in organoid culture. The ECM gels demonstrate excellent physiological and mechanical properties while having the proteomic signature of endoderm tissue with specific enrichment of key ECM proteins relevant to organoid formation.

A device for simulating a function of a tissue includes a first structure, a second structure, and a membrane. The first structure defines a first chamber. The first chamber includes a matrix disposed therein and an opened region. The second structure defines a second chamber. The membrane is located at an interface region between the first chamber and the second chamber. The membrane includes a first side facing toward the first chamber and a second side facing toward the second chamber. The membrane separates the first chamber from the second chamber.