Differentiation of human embryonic stem cells
First Claim
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1. A method for increasing insulin in a patient having Type 1 diabetes comprising:
- and differentiating pancreatic endoderm cells into a population of pancreatic endocrine cells by culturing pancreatic endoderm cells in medium supplemented with glucose at a concentration from about 10 mM to about 20 mM and treating with a factor selected from the group consisting of;
a gamma secretase inhibitor, Exendin-4, and a combination of Exendin-4 and hepatocyte growth factor; and
providing the population of pancreatic endocrine cells to the patient, wherein the cells are provided by implanting encapsulated cells into the liver or by infusing the cells into the hepatic portal vein, wherein cells in the population of pancreatic endocrine cells express insulin.
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Abstract
The present invention provides methods to promote the differentiation of pluripotent stem cells. In particular, the present invention provides an improved method for the formation of pancreatic endoderm, pancreatic hormone expressing cells and pancreatic hormone secreting cells. The present invention also provides methods to promote the differentiation of pluripotent stem cells without the use of a feeder cell layer.
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Citations
16 Claims
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1. A method for increasing insulin in a patient having Type 1 diabetes comprising:
and differentiating pancreatic endoderm cells into a population of pancreatic endocrine cells by culturing pancreatic endoderm cells in medium supplemented with glucose at a concentration from about 10 mM to about 20 mM and treating with a factor selected from the group consisting of;
a gamma secretase inhibitor, Exendin-4, and a combination of Exendin-4 and hepatocyte growth factor; andproviding the population of pancreatic endocrine cells to the patient, wherein the cells are provided by implanting encapsulated cells into the liver or by infusing the cells into the hepatic portal vein, wherein cells in the population of pancreatic endocrine cells express insulin. - View Dependent Claims (5, 6, 7, 8, 9)
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2. A method for increasing insulin in a patient having Type 1 diabetes comprising:
differentiating human pluripotent stem cells into definitive endoderm cells by treating the human pluripotent stem cells with activin A; differentiating the definitive endoderm cells into pancreatic endoderm cells by treating the definitive endoderm cells with at least one fibroblast growth factor, or with retinoic acid and at least one fibroblast growth factor; differentiating the pancreatic endoderm cells into a population of pancreatic endocrine cells by culturing the pancreatic endoderm cells in medium supplemented with glucose at a concentration from about 10 mM to about 20 mM and treating with a factor selected from the group consisting of;
a gamma secretase inhibitor, Exendin-4, and a combination of Exendin-4 and hepatocyte growth factor; andproviding the population of pancreatic endocrine cells to the patient, wherein the population is provided by implanting encapsulated cells into the liver or by infusing the cells into the hepatic portal vein, and wherein cells in the population express insulin. - View Dependent Claims (3, 4, 10, 11, 12)
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13. A method for increasing insulin in a patient having Type 1 diabetes comprising:
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generating a population of human pancreatic endocrine cells in which cells express insulin by culturing pancreatic endoderm cells in medium supplemented with glucose at a concentration from about 10 mM to about 20 mM and treating with a factor selected from the group consisting of;
a gamma secretase inhibitor, Exendin-4, and a combination of Exendin-4 and hepatocyte growth factor; andproviding the population of endocrine cells to the patient by implanting encapsulated cells into the liver or by infusing cells into the hepatic portal vein. - View Dependent Claims (14, 15, 16)
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Specification