Abstract: We describe a robust human adult distal lung organoid method with a procedure for everting organoids to essentially turn them inside out. This then relocates the apical ACE2-expressing surfaces of cells to the organoid exterior, where they can then be easily infected by SARS-CoV-2 added to the tissue culture medium. Further, this method can be used for infection of any distal lung pathogen that infects apically. Alternatively, if a pathogen interacts basolaterally then eversion is not necessary, and the human adult distal lung organoids can be infected as is.

A method for producing astrocytes includes a step of dissociating an embryoid body into single cells and suspension-culturing the cells in a serum-free medium containing basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) to obtain a neural stem cell mass, and a step of dissociating the neural stem cell mass into single cells and adhesion-culturing the cells in a serum-free medium to obtain a cell population containing astrocytes.

An in vitro microfluidic gut-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 culture is described, allowing for interactions between lamina propria-derived cells and gastrointestinal epithelial cells and endothelial cells. This in vitro microfluidic system can be used for modeling inflammatory gastrointestinal tissue, e.g., Crohn's disease, colitis and other inflammatory gastrointestinal disorders. These multicellular, layered microfluidic gut-on-chip further allow for comparisons between types of gastrointestinal tissues, e.g., small intestinal deuodejeum, small intestinal ileium, 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.

The present invention relates to three-dimensional (3D) tissue constructs and methods of using such 3D tissue constructs to screen for neurotoxic agents. In particular, provided herein are methods of producing and using complex, highly uniform human tissue models comprising physiologically relevant human cells, where the tissue models have the degree of sample uniformity and reproducibility required for use in quantitative high-throughput screening applications.

This invention relates to culture methods and media for in vitro expansion of hepatocytes, particularly primary hepatocytes; hepatocyte cultures and organoids obtainable and obtained by said methods; and uses of said hepatocyte cultures and organoids.

Sebaceous gland-like organoids comprising a Blimp1 positive cell are provided. Methods of producing the organoids and using the organoids to test a skin drug are also provided; as are methods of treating acne.

Compositions and systems comprising a dorsal forebrain organoid having a core comprising less than 25% apoptotic or hypoxic cells and one or more tumor cells in the organoid.

A method of in vitro cellular assay includes measuring an electrical activity of at least two cell populations in a plurality of cell populations that are disposed to be spaced apart from each other and connected to each other via a neurite, in which at least one of the at least two cell populations for which the electrical activity is measured is a cell population including at least one kind of neural cell, and the at least two cell populations each exhibit different electrical activity properties at a point when the electrical activity is measured.

An in vitro population of human brain endothelial cells (hBECs) expressing claudin-5, occludin, ZO-1 and GLUT-1 and expressing one or more of FZD7, WNT7A, WNT7B, APCDD1, STRA6 and ZO-3 is provided. A blood brain barrier (BBB) comprising the hBECs and use of the BBB for analyzing permeability characteristics of a test agent are provided.

Methods for mimicking a tumor microenvironment in vitro are provided. The methods comprise indirectly applying a shear stress upon at least one tumor cell type plated on a surface within a cell culture container. Methods for mimicking tumor metastasis and methods for testing drugs or compounds in such systems are also provided.