Differentiation of pancreatic endocrine cells
AssigneeVertex Pharmaceuticals Incorporated
InventorsGeorge Harb, Chunhui Xie
Life of this patent
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Abstract
Disclosed herein are compositions and methods related to differentiation of stem cells into pancreatic endocrine cells. In some aspects, the methods provided herein relate to generation of pancreatic β cell, α cell, δ cells, and EC cells in vitro. In some aspects, the disclosure provides pharmaceutical compositions including the cells generated according to the methods disclosed herein, as well as methods of treatment making use thereof.
Claims35
-30. (canceled)
A method, comprising:
- (a) contacting a plurality of PDX1-positive, NKX6.1-negative pancreatic progenitor cells with one or more of a ROCK inhibitor, a growth factor from TGFβ superfamily, a growth factor from FGF family, a RA signaling pathway activator, and a SHH pathway inhibitor, thereby generating a first population of cells;
- (b) contacting the first population of cells with a PKC activator and a γ-secretase inhibitor and one or more of a ROCK inhibitor, a growth factor from the TGFβ superfamily, a growth factor from the FGF family, a RA signaling pathway activator, and a SHH pathway inhibitor, thereby generating a second population of cells;
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- (c) contacting the second population of cells with a PKC activator, a γ-secretase inhibitor and one or more of a TGF-β signaling pathway inhibitor, a growth factor from EGF family, a RA signaling pathway activator, a SHH pathway inhibitor, a TH signaling pathway activator, a protein kinase inhibitor, a ROCK inhibitor, a BMP signaling pathway inhibitor, and an epigenetic modifying compound, thereby generating a third population of cells.
-89. (canceled)
An in vitro composition, comprising PDX1-positive, NKX6.1-negative pancreatic progenitor cells;
- PDX1-positive, NKX6.1-positive pancreatic progenitor cells;
- a PKC activator;
- and a γ-secretase inhibitor.
-136. (canceled)
An in vitro composition comprising PDX1-positive cells, a γ-secretase inhibitor, and one or both of a growth factor from the TGFβ superfamily and a growth factor from the FGF family.
-166. (canceled)
A population of in vitro differentiated cells comprising NKX6.1-positive, ISL1-positive cells and NKX6.1-negative, ISL1-positive cells;
- and wherein less than 12% of the cells in the population are NKX6.1-negative, ISL1-negative cells.
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Dependencies are inferred from the claim text.