In vitro differentiation of pluripotent stem cells to pancreatic endoderm cells (PEC) and endocrine cells
AssigneeViaCyte, Inc.
InventorAlan D. Agulnick
Life of this patent
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Abstract
A human immature endocrine cell population and methods for making an immature endocrine cell population are provided. Specifically, immature beta cells and methods for production of immature beta cells are described. Immature beta cells co-express INS and NKX6.1 and are uni-potent and thereby develop into mature beta cells when implanted in vivo. The mature beta cells in vivo are capable of producing insulin in response to glucose stimulation.
Claims20
A method of producing Chromogranin A (CHGA)-negative cells comprising, contacting human definitive endoderm lineage cells in vitro with a TGFβ superfamily member and a Wnt family member thereby producing CHGA-negative cells.
A method for producing mature beta cells in vivo, said method comprising:
- a) contacting human definitive endoderm lineage cells in vitro with a TGFβ superfamily member and a Wnt family member, thereby producing CHGA-negative cells;
- b) differentiating the CHGA-negative cells into immature beta cells;
- c) transplanting the immature beta cells of step (b) into a mammalian subject;
- d) allowing the immature beta cells to mature in vivo to produce a population of cells comprising insulin secreting beta cells.
A method of producing unipotent human immature beta cells comprising:
- a) contacting human definitive endoderm lineage cells in vitro with Activin A and Wnt3a, thereby producing CHGA-negative cells, and then
- b) differentiating the CHGA-negative cells into unipotent human immature beta cells.
Dependencies are inferred from the claim text.