DIFFERENTIATED HUMAN LIVER CELL CULTURES AND THEIR USE IN BIOARTIFICIAL LIVER SYSTEMS

摘要

Human hepatocyte cell cultures and their use in bioreactors and bioartificial liver (BAL) systems are provided. The cells have constitutive liver-specific metabolic activity resembling that of freshly isolated human hepatocytes. The hepatocyte cells and BAL systems can be used to treat patients suffering from acute liver failure, end-stage liver disease, or acute-on-chronic liver disease.

主权项

1. A cell culture comprising differentiated cells from a human hepatocyte cell line in a suitable culture medium, wherein said differentiated cells have constitutive liver-specific metabolic activity, the cell culture being obtained by a process comprising:
selecting a human hepatocyte cell line; a phase of cell proliferation comprising culturing cells of said human hepatocyte cell line in a suitable culture medium, preferably comprising serum, hormones, growth-factors and antibiotics; loading viable cells to an amount of at least 5% of normal liver mass in a bioreactor comprising a three dimensional support matrix, and allowing the cells to attach to said matrix; an expansion or proliferation phase comprising culturing the cells loaded in the bioreactor in a suitable culture medium, preferably comprising serum, hormones, growth-factors and antibiotics, to achieve at least one cell population doubling; and a phase of cell differentiation comprising culturing the cells in a culture medium comprising serum, hormones, growth factors and antibiotics.