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US 11,952,591 B2Granted
Generation of human pluripotent stem cell derived functional beta cells showing a glucose-dependent mitochondrial respiration and two-phase insulin secretion response
AssigneeJanssen Biotech, Inc.
InventorsSebastian Rieck, Alireza Rezania
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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.
Claims19
A method of producing functional beta cells, comprising:
- culturing pancreatic immature beta cells in a medium comprising:
- a) an effective amount of T3 or T4;
- and
- b) an effective amount of 5-Azacytidine (AZT), 3-Deazaneplanocin A (DEZA), or a combination thereof,
- thereby producing functional beta cells that express insulin, wherein the functional beta cells consume oxygen in response to glucose simulation at a higher rate than functional beta cells produced in the absence of the medium.
2 more elements
A method of producing functional beta cells, comprising:
- culturing pancreatic immature beta cells in a medium comprising:
- a) an effective amount of T3 or T4;
- and
- b) an effective amount of 5-Azacytidine (AZT), 3-Deazaneplanocin A (DEZA), or a combination thereof,
- and wherein the medium does not comprise an ALK5 inhibitor, thereby producing functional beta cells that express insulin.
2 more elements
Dependencies are inferred from the claim text.