Human hepatic progenitor cells and methods of use thereof
OwnerSuchitra Holgerssoninventor
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Abstract
Liver progenitor cells immunoreactive for CD117, as well as for CD34 capable of proliferating in a culture; and differentiating in vivo into a hepatocyte, a cholangiocyte or a sinusoidal cell are provided. The cultures can be expanded over a large number of passages and integrate well after transplantation into adult liver.
Claims22
An in vitro cell culture comprising cells derived from liver tissue of a human, wherein said cells in the culture are
- a. CD117+, CD34+, and Lin−;
- b. capable of proliferating in a culture;
- and
- c. capable of differentiating in vivo into a hepatocyte, a cholangiocyte or a sinusoidal cell.
A method of producing a human liver sinusoidal cell in vitro comprising
- a. providing a cell suspension comprising a CD117+, CD34+, and Lin− cell;
- b. culturing the cell suspension;
- and
- c. differentiating the cell progeny in a culture medium containing vascular endothelial growth factor.
A method of producing a human liver hepatocyte, or cholangiocyte in vitro comprising
- a. providing a cell suspension comprising a CD117+, CD34+, and Lin− cell;
- b. culturing the cell suspension;
- and
- c. differentiating the cell progeny in a culture medium containing EGF and HGF.
A method of producing a population of human liver progenitor cells which differentiate in vivo into hepatocytes, or cholangiocytes or sinusoidal cells, comprising selecting from a population of human liver derived cells for cells that are CD117+, CD34+, and Lin−.
A method transplanting multipotent liver progenitor cell progeny to a host comprising
- a. providing an in vitro cell culture comprising multipotential human CD117+, CD34+, and Lin− liver progenitor cells wherein said cells maintain multipotential capacity to differentiate into hepatocytes, cholangiocytes or sinusoidal cells;
- and
- b. transplanting said cells in said host.
A method of screening for compounds which effect proliferation, differentiation or survival of liver cells comprising
- a. providing an in vitro cell culture comprising multipotential human CD117+, CD34+, and Lin− liver progenitor cells wherein said cells maintain multipotential capacity to differentiate into hepatocytes, cholangiocytes or sinusoidal cells;
- b. contacting said culture with a test compound;
- and
- c. determining if said compound has an effect on proliferation proliferation, differentiation or survival of liver cells
An in vitro method for determining a metabolite of a test compound comprising
- a. providing an in vitro cell culture comprising multipotential human CD117+, CD34+, and Lin− liver progenitor cells wherein said cells maintain multipotential capacity to differentiate into hepatocytes, cholangiocytes or sinusoidal cells;
- b. contacting said culture with the test compound;
- and
- c. identifying a metabolites derived from the test compound after incubation with said culture.
An in vitro method of determining the anti-viral activity of a test compound comprising:
- a. providing an in vitro cell culture comprising multipotential human CD117+, CD34+, and Lin− liver progenitor cells wherein said cells maintain multipotential capacity to differentiate into hepatocytes, cholangiocytes or sinusoidal cells;
- b. contacting said culture with a virus and a test compound;
- and
- c. comparing the survival rate of said culture with a control cell culture;
- wherein in an increase in survival rate of said culture compared to said control culture indicates anti-viral activity of said test compound
An in vitro method of determining the infectivity of a virus comprising:
- a. providing an in vitro cell culture comprising multipotential human CD117+, CD34+, and Lin− liver progenitor cells wherein said cells maintain multipotential capacity to differentiate into hepatocytes, cholangiocytes or sinusoidal cells;
- b. contacting said culture with a virus;
- and
- c. determining if said virus has an effect in proliferation or survival of the cells in the cell culture.
Dependencies are inferred from the claim text.