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.

Disclosed are methods for making a vascularized hollow organ derived from human intestinal organoid (HIOs). The HIOs may be obtained from human embryonic stem cells (ESC's) and/or induced pluripotent stem cells (iPSCs), such that the HIO forms mature intestinal tissue. Also disclosed are methods for making a human intestinal tissue containing a functional enteric nervous system (ENS).

According to one embodiment, a pluripotent stem cell manufacturing system includes processing circuitry. The processing circuitry acquires storage information for the storage of a sample from a donor, and surviving cell number information for the number of surviving cells contained in the sample. The processing circuitry estimates tissue stem cell number information for the number of tissue stem cells contained in the sample, based on the storage information and the surviving cell number information.

Disclosed are methods of assessing the ability of a candidate therapeutic agent to reverse, reduce or prevent intestinal injury by a potential toxic agent using a three-dimensional, engineered, bioprinted, biological intestinal tissue model. Also disclosed are methods of assessing the effect of an agent on intestinal function, the method comprising contacting the agent with a three-dimensional, engineered, bioprinted, biological intestinal tissue model.

A population of enteroendocrine cells (EEC) is obtained from a mammalian post-natal cell population, such as a population including post-natal stem cells, by treating the population with a plurality of small molecules that upregulate ChgA and promote differentiation of the cells to form the enteroendocrine cells. The upregulation of ChgA is such that the fraction of cells expressing CGA in the obtained cell population, as measured by a ChgA Immunostaining Assay, is at least about 1.5%. Small molecules that can be used to differentiate the post-natal cells into the enteroendocrine cells can include at least one of a Wnt activator, a Notch inhibitor, a Wnt inhibitor, a MEK/ERK inhibitor, a growth factor, a HDAC inhibitor, a Histone Methylation Inhibitor, a Tgf-β inhibitor, and a NeuroD1 activator. Also, the insulin expression of a population of mammalian cells is increased by treating the population with a plurality of small molecules that increase the insulin expression.

The present invention relates to an in vitro method of culturing a segmented filamentous bacterium strain, comprising co-culturing said segmented filamentous bacterium strain with a eukaryotic host cell, wherein the culture is performed at an O.sub.2 level inferior to 5% in a rich tissue culture liquid medium containing bacterial medium components including iron. The present invention also relates to methods for genetically modifying a segmented filamentous bacterium strain comprising a step a culturing the strain in vitro.

Disclosed are methods for making a vascularized hollow organ derived from human intestinal organoid (HIOs). The HIOs may be obtained from human embryonic stem cells (ESC's) and/or induced pluripotent stem cells (iPSCs), such that the HIO forms mature intestinal tissue. Also disclosed are methods for making a human intestinal tissue containing a functional enteric nervous system (ENS).

Disclosed are methods of assessing the ability of a candidate therapeutic agent to reverse, reduce or prevent intestinal injury by a potential toxic agent using a three-dimensional, engineered, bioprinted, biological intestinal tissue model. Also disclosed are methods of assessing the effect of an agent on intestinal function, the method comprising contacting the agent with a three-dimensional, engineered, bioprinted, biological intestinal tissue model.

The present disclosure provides methods and formulations for treating a patient suffering from one or more of chronic inflammatory injury, metaplasia, dysplasia or cancer of an epithelial tissue, which method comprises administering to the patient an agent that selectively kills or inhibits the proliferation or differentiation of pathogenic epithelial stem cells (PESCs) relative to normal epithelial stem cells in the tissue in which the PESCs are found. Representative epithelial tissues include pulmonary, genitourinary, gastrointestinal/esophageal, pancreatic and hepatic tissues.

There is provided a novel method for culturing a hepatic epithelioid tissue. The method uses a method for forming a hepatic epithelioid tissue having a structure of connections between hepatocytes and bile duct epithelial cells, comprising a step of culturing bile duct epithelial cells on a collagen gel, and a step of inoculating and culturing hepatocytes on the cultured bile duct epithelial cells.