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AssigneeRutgers, The State University of New Jersey
InventorsHatim SABAAWY, Fredrick E. WONDISFORD
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Liver metabolism studies are limited by the inability to expand primary hepatocytes in vitro while maintaining their metabolic functions. Human hepatic three dimensional organoids have been established for use in these studies, but hepatic organoids from adult donors had impaired expansion. Methods of achieving expansion of adult donor-derived hepatic organoids (HepAOs) and HepG2 cells (HepGOs) from single cells in organoid cultures using combinations of growth factors and small molecules are described, with assessment of expansion dynamics, gluconeogenic and HNF4α expression, and albumin secretion. The invention discloses conditions including limiting A8301 and incorporating FSK and OSM to allow the expansion of HepAOs from adult donors and HepGOs with gluconeogenic competence. These models increase the repertoire of human hepatic cellular tools available for use in liver metabolic assays.
An isolated hepatocyte in three-dimensional culture, which is derived from a donor adult hepatic cell or a hepatoma, and which is gluconeogenic.
A method of producing a liver organoid in serum-free three-dimensional culture conditions, comprising:
Dependencies are inferred from the claim text.