Methods for production of functional beta cells
First Claim
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1. A method of maturing an immature pancreatic beta cell into a mature pancreatic beta cell expressing PDX1, NKX6.1, MAFA, UCN3 and SLC2A1 comprising:
- culturing the immature pancreatic beta cell in a medium supplemented with one or more of UNC0638, UNC0642, UNC0646, TC-E5003, A366, PF03814735, ZM447439, SB747651A, PFI1, LY303511, MS436, AZT, DEZA, pyroxamide, CI9994 or MC1568, thereby maturing the immature pancreatic beta cell into the mature beta cell.
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Abstract
The invention provides for methods of differentiating pancreatic endocrine cells into pancreatic beta cells expressing PDX1, NKX6.1, MAFA, UCN3 and SLC2A. These pancreatic beta cells may be obtained by step-wise differentiation of pluripotent stem cells. The pancreatic beta cells exhibit glucose-dependent mitochondrial respiration and glucose-stimulated insulin secretion similar to islet cells.
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Citations
43 Claims
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1. A method of maturing an immature pancreatic beta cell into a mature pancreatic beta cell expressing PDX1, NKX6.1, MAFA, UCN3 and SLC2A1 comprising:
culturing the immature pancreatic beta cell in a medium supplemented with one or more of UNC0638, UNC0642, UNC0646, TC-E5003, A366, PF03814735, ZM447439, SB747651A, PFI1, LY303511, MS436, AZT, DEZA, pyroxamide, CI9994 or MC1568, thereby maturing the immature pancreatic beta cell into the mature beta cell. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 41)
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12. A method of differentiating pluripotent stem cells into mature beta cells expressing PDX1, NKX6.1, MAFA, UCN3 and SLC2A:
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a) differentiating pluripotent stem cells into definitive endoderm cells; b) differentiating the definitive endoderm cells of step a) into primitive gut tube cells; c) differentiating the primitive gut tube cells of step b) into foregut endoderm cells; d) differentiating the foregut endoderm cells of step c) into pancreatic endoderm cells; e) differentiating the pancreatic endoderm cells of step d) into pancreatic endocrine precursor cells; f) differentiating the pancreatic endocrine precursor cells of step e) into immature beta cells; and g) culturing the immature beta-cells of step f) in a medium supplemented with one or more of UNC0638, UNC0642, UNC0646, TC-E5003, A366, PF03814735, ZM447439, SB747651A, PFI1, LY303511, MS436, AZT, DEZA, pyroxamide, CI9994 or MC1568 to mature the immature beta cells into the mature beta cells expressing PDX1, NKX6.1, MAFA, UCN3 and SLC2A1. - View Dependent Claims (13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 42, 43)
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Specification