The present disclosure relates to methods for expanding populations of hematopoietic stem cells (HSCs) using a genetically engineered human fetal liver niche and compositions of purified ex vivo expanded HSCs. Also provided herein are methods of using such expanded HSC cell populations for clinical applications including allogeneic hematopoietic stem cell transplantation and for drug discovery and modeling human liver development.

The present invention provides a method for artificially producing a vascular endothelial stem cell from a non-vascular endothelial stem cell. The method for producing a vascular endothelial stem cell of the present invention comprises the step of bringing a vascular endothelial cell possessing no stem cell properties into contact with a factor secreted by an organ of a neonatal or juvenile mammal. The step may be a step of (1) transplanting the vascular endothelial cell possessing no stem cell properties into the organ of the neonatal or juvenile mammal, wherein the mammal is a non-human mammal, or (2) culturing the vascular endothelial cell possessing no stem cell properties in a culture system containing the factor secreted by the organ of the neonatal or juvenile mammal.

The instant disclosure relates to compositions derived from precursor cells, and methods of using such compositions, for the manufacture of hematopoietic stem cells (HSCs) or derivative immune cells. More particularly, methods for obtaining hematopoietic stem cells from organoid tissue or cultures comprising organoids are disclosed, wherein the organoid tissue or cultures comprise liver or colonic tissue derived from precursor cells (such as embryonic stem cells or induced pluripotent stem cells), via directed differentiation.

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.

Microfluidic devices for modeling three-dimensional tissue structures and methods for making and using the same are described herein.

Engineered, living, three-dimensional liver tissue constructs including: one or more layers, wherein each layer contains one or more liver cell types, the one or more layers cohered to form a living, three-dimensional liver tissue construct free of pre-formed scaffold. Also disclosed are arrays and methods of making the same.

There is described an isolated 3-dimensional liver spheroid wherein said spheroid has: increased ATP content as compared to a 3-dimensional liver spheroid cultured in Complete William's E medium alone; the same or increased activity of cytochrome P450 1A1 and cytochrome P450 1B1 as compared to a 3-dimensional liver spheroid cultured in Complete William's E medium alone; and increased albumin secretion as compared to a 3-dimensional liver spheroid cultured in William's E medium alone.

Microfluidic devices for modeling three-dimensional tissue structures and methods for making and using the same are described herein.

Inducible engineered tissue constructs comprising at least one cell population comprising a genetic construct are provided. Methods of making and using said constructs are also provided.

The present invention provides a co-culture system and method for assessing cellular cholesterol (Choi) efflux and uptake in vitro. The co-culture system mimics in vivo Choi efflux and uptake in the context of mammalian physiology. The methods and systems provided can be used in some embodiments to evaluate the effect of a pharmacological agent on cellular Choi efflux and uptake or for diagnostic purposes.