The invention in general relates to human hepatic 3D co-culture models, more in particular 3D spheroid co-cultures of human hepatocyte-like cells and hepatic stellate cells. Furthermore, the invention provides a method for obtaining such co-cultures, as well as the use of said co-cultures in the identification of pro-fibrotic and/or anti-fibrotic compounds.

The present invention is long-term cultures of avian PGCs and techniques to produce germline chimeric and transgenic birds derived from prolonged PGC cultures. In some embodiments, these PGCs can be transfected with genetic constructs to modify the DNA of the PGC, specifically to introduce a transgene encoding an exogenous protein. When combined with a host avian embryo by known procedures, those modified PGCs are transmitted through the germline to yield transgenic offspring. These germline chimeric birds do not have substantial contributions of PGC-derived phenotypes in somatic cells or tissues. This invention includes compositions comprising long-term cultures of PGCs that can be genetically modified by gene targeting, that can accept large amounts of foreign DNA and that contribute to the germline of recipient embryos.

The invention is directed to three-dimensional, engineered, bioprinted biological tissue constructs exhibiting a liver disorder, methods of making the constructs, and use of the constructs in assays, such as drug testing and molecular diagnostic testing, including methods of assessing the ability of a candidate therapeutic agent to reverse, reduce, or prevent a liver disorder, and methods for biomarker discovery.

A cell culturing device has: a first culture chamber; a first introduction flow channel and a first discharge flow channel which are connected to the first culture chamber; a second culture chamber connected to a halfway part of the first introduction flow channel via a first porous membrane; and a second introduction flow channel and a second discharge flow channel which are connected to the second culture chamber. The first discharge flow channel is connected to the first culture chamber via a second porous membrane. The first introduction flow channel has a liquid collecting part between the first culture chamber and the second culture chamber.

Immunotolerant engineered human tissue constructs are provided that are suitable for implantation into subjects. In some embodiments, the immunotolerance is controllable by an inducible system. Methods of making and using the immunotolerant engineered tissue constructs are provided.

Disclosed herein are hepato-biliary-pancreatic organoid (HBPO or HBP organoid) compositions, and methods of making and using hepato-biliary-pancreatic organoid compositions. The disclosed compositions may have two or more functions selected from hepatic tissue function, biliary tissue function, exocrine pancreatic function, and endocrine pancreatic tissue function. Methods of treating individuals using the hepato-biliary-pancreatic organoid compositions is also disclosed.

An object of the present invention is to provide, for example, a therapeutic agent for hepatic disorders using a specific mesenchymal stem cell line derived from an adipose tissue (ASCL), the therapeutic agent being capable of being preserved and stably supplied and having a better therapeutic effect on hepatic disorders. A feature of the present invention is to use a mesenchymal stem cell line derived from an adipose tissue, the mesenchymal stem cell line having been produced by a production method comprising: (A) inducing differentiation of one or more cells selected from a stromal vascular fraction of a vertebrate animal adipose tissue comprising a mesenchymal stem cell, an adipose progenitor cell, and a stromal cell into a mature adipocyte; and (B) inducing dedifferentiation of the mature adipocyte obtained in step (A) to obtain a mesenchymal cell line derived from the vertebrate animal adipose tissue.

The present invention provides a simple and robust human liver cell-based system in which persistent hepatitis C infection, persistent hepatitis B infection or ethanol exposure induces a clinical Prognostic Liver Signature (PLS) high-risk gene signature. The cellular model system for hepatocellular carcinoma (HCC)/cirrhosis development and progression may be used in the screening of compounds useful in the treatment and/or prevention of cirrhosis and/or HCC as well as in the identification biomarkers for the prediction of liver disease (especially cirrhosis) progression and HCC. The present invention also relates to specific compounds that have been identified, using such screening methods, as useful in the treatment and/or the prevention of HCC/cirrhosis.

Disclosed herein are hepato-biliary-pancreatic organoid (HBPO or HBP organoid) compositions, and methods of making and using hepato-biliary-pancreatic organoid compositions. The disclosed compositions may have two or more functions selected from hepatic tissue function, biliary tissue function, exocrine pancreatic function, and endocrine pancreatic tissue function. Methods of treating individuals using the hepato-biliary-pancreatic organoid compositions is also disclosed.

A feeder cell for maintaining or proliferating, by a two-dimensional culture, a cell deemed to be difficult to maintain and proliferate by a two-dimensional culture; and a method of producing the feeder cell. A fibroblast-like cell is produced from a pluripotent stem cell, and derived from an intestinal structure containing an endoderm-derived cell and a mesoderm-derived cell is proliferated, isolated, and used as a feeder cell.