HOMOGENEOUS DIFFERENTIATION OF HEPATOCYTE-LIKE CELLS FROM EMBRYONIC STEM CELLS
First Claim
1. A method to differentiate pluripotent stem (PS) cells into mature functional hepatocytes, comprising:
- (a) differentiating PS cells into monolayer colonies of early endodermal cell populations, and(b) maturating of the endodermal cell population into hepatic lineage cells expressing hepatocyte lineage markers and/or demonstrating hepatocyte function.
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Abstract
One of the major hurdles of cellular therapies for the treatment of liver failure is the low availability of functional human hepatocytes. Although embryonic stem (ES) cells represent a potential cell source for therapy, current methods for differentiation result in mixed cell populations or low yields of the cells of interest. The present invention provides for a rapid, direct differentiation method that yields a homogeneous population of endoderm-like cells with 95% purity. In one embodiment, mouse ES cells cultured on top of collagen-sandwiched hepatocytes differentiate and proliferate into a uniform and homogeneous cell population of endoderm-like cells. The endoderm-like cell population was positive for Foxa2, Sox17 and AFP, and could further differentiate into hepatocyte-like cells that demonstrate hepatic morphology, functionality, and gene and protein expression. Incorporating the hepatocyte-like cells into a bioartificial liver device to treat fulminant hepatic failure improved animal survival, thereby underscoring the therapeutic potential of these cells.
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Citations
14 Claims
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1. A method to differentiate pluripotent stem (PS) cells into mature functional hepatocytes, comprising:
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(a) differentiating PS cells into monolayer colonies of early endodermal cell populations, and (b) maturating of the endodermal cell population into hepatic lineage cells expressing hepatocyte lineage markers and/or demonstrating hepatocyte function. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14)
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Specification