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US 10,870,832 B2Granted
Use of small molecules to enhance MAFA expression in pancreatic endocrine cells
AssigneeJanssen Biotech, Inc.
InventorAlireza Rezania
Life of this patent
Estimating the term…
Abstract
The present invention provides methods, cell cultures and differentiation media to promote differentiation of pluripotent stem cells to pancreatic endocrine cells of a mature phenotype. The resulting pancreatic endocrine cells express single hormonal insulin, PDX1, NKX6.1, and MAFA. In one or more differentiation stages, culturing may be carried out in a culture vessel at the air-liquid interface.
Claims16
A method for producing pancreatic endocrine cells expressing MAFA comprising:
- (a) obtaining a population of cells comprising pancreatic endoderm and endocrine precursor cells;
- (b) differentiating the population of cells comprising pancreatic endoderm and endocrine precursor cells into a pancreatic endocrine cell population in a medium comprising (i) a SHH signaling pathway antagonist, (ii) a BMP inhibitor, (iii) T3, a T3 analogue, T4, a T4 analogue or a mixture thereof, and (iv) an ALK5 inhibitor;
- and
- (c) culturing the pancreatic endocrine cell population in a further medium comprising an aurora kinase inhibitor, an RSK inhibitor, an inhibitor of protein methyltransferase DOT 1L, or a combination thereof.
1 more element
A method for producing a pancreatic endocrine cell population expressing MAFA, comprising:
- (a) obtaining a pancreatic endoderm and endocrine precursor cell population;
- and
- (b) culturing the pancreatic endoderm and endocrine precursor cell population in a medium, wherein the medium comprises (i) a SMO inhibitor or a SHH signaling pathway antagonist, (ii) a BMP inhibitor, (iii) T3, an analogue of T3, T4, an analogue of T4 or a mixture thereof, (iv) an ALK5 inhibitor, and (v) an aurora kinase inhibitor, an RSK inhibitor, an inhibitor of protein methyltransferase DOT1L, or a combination thereof,
- thereby producing the pancreatic endocrine cell population, wherein cells in the pancreatic cell endocrine population express MAFA.
1 more element
Dependencies are inferred from the claim text.