The present invention relates to a cell structure including cells containing at least hepatocytes and vascular endothelial cells, and extracellular matrix component, wherein the extracellular matrix components are disposed between the cells, and a liver sinusoidal network is provided between the cells.

The present invention provides methods for assessing a compound's potential toxicity.

Provided is a 3D human liver organ model constructing method, comprising: preparing human primary liver cells, or mixed cells of same and liver non-parenchymal cells, or human liver cancer cell lines into a single cell suspension, and mixing the single cell suspension with a matrix material to obtain a mixed cell suspension; inoculating the mixed cell suspension into cultivation micropores of a 3D organ-on-a-chip, and carrying out cultivation at 37° C. to obtain a gelled 3D organ-on-a-chip; adding a culture medium into liquid storage holes of the organ-on-a-chip, and carrying out cultivation to obtain a 3D human liver organ model. Compared with other 2D human liver organ models, the constructed 3D human liver organ model has significantly enhanced response sensitivity to hepatotoxic drugs, and shows stronger hepatotoxic damage effect for reported hepatotoxic drugs. Compared with an animal model, the 3D human liver organ model can effectively eliminate the screening difference caused by species difference.

A developmental toxicity screening assay using spatially organized cardiac organoids with contracting cardiomyocytes in the center surrounded by stromal cells distributed along the pattern perimeter engineered from human induced pluripotent stem cells (hiPSCs). Cardiac organoids generated from 600 μm-diameter circles were used as a developmental toxicity screening assay for the quantification of the embryotoxic potential of nine pharmaceutical compounds. The cardiac organoids were demonstrated as having a potential use as an in vitro platform for studying organoid structure-function relationships, developmental processes, and drug-induced cardiac developmental toxicity.

A cell culture substrate having a high cell-adhesion portion and a low cell-adhesion portion, wherein; an adhesiveness to a cell of the high cell-adhesion portion and an adhesiveness to a cell of the low cell-adhesion portion are different from each other, the adhesiveness to the cell of the high cell-adhesion portion to cells is higher than the adhesiveness of the low cell-adhesion portion to the cell; and the high cell-adhesion portion has a cell adhesion layer containing two or more kinds of cell adhesion substances on the surface.

Compositions, devices and methods are described for improving adhesion, attachment, and/or differentiation of cells in a microfluidic device or chip. In one embodiment, one or more ECM proteins are covalently coupled to the surface of a microchannel of a microfluidic device. The microfluidic devices can be stored or used immediately for culture and/or support of living cells such as mammalian cells, and/or for simulating a function of a tissue, e.g., a liver tissue, muscle tissue, etc. Extended adhesion and viability with sustained function over time is observed.

Provided are methods for determining the risk of toxicity (e.g., neurotoxicity) and/or the likelihood of response to a cell therapy. In some aspects, the methods generally involve assessing parameters or biomarkers (e.g., blood analytes) that are associated with toxicity and/or response. In some aspects, the methods relate to adoptive cell therapy involving the administration of doses of cells for treating subjects with certain B cell malignancies, such as chronic lymphocytic leukemia (CLL), such as relapsed or refractory CLL, or small lymphocytic lymphoma (SLL). The cells for the adoptive cell therapy generally express recombinant receptors such as chimeric antigen receptors (CARs). In some aspects, the methods can be used to identify or select subjects for treatment, for example, with a cell therapy.

The invention is directed to methods for culturing cells so that the cells are induced to differentiate into cells that express a hepatic stellate phenotype. The invention is also directed to cells produced by the methods of the invention. The cells are useful, among other applications, for treatment of liver deficiencies, liver metabolism studies, and liver toxicity studies, fibrogenic studies, or to support hepatocyte function in co-culture setting.

The present disclosure provides an encapsulated liver tissue that can be used in vivo to improve liver functions, in vitro to determine the hepatic metabolism and/or hepatotoxicity of an agent and ex vivo to remove toxic compounds from patients' biological fluid. The encapsulated liver tissue comprises at least one liver organoid at least partially covered with a biocompatible cross-linked polymer. Processes for making the encapsulated liver tissue are also provided.

Provided herein are compositions and methods for reducing toxicity associated with TAR DNA-binding protein 43. Certain embodiments of the present disclosure are related to compositions that treat, inhibit, reduce, prevent, or delay a disease or condition associated with TDP-43 toxicity, such as cystic fibrosis or neurodegenerative diseases. Certain embodiments of the present disclosure are related to methods of treating, inhibiting, reducing, preventing, or delaying a disease or condition associated with TDP-43 toxicity by administering compounds of any one of Formulas (I), (II), (III), (IV), (V), (VI), (VII), or (VIII) to a subject in need.