SC-beta cells and compositions and methods for generating the same
AssigneePresident and Fellows of Harvard College
InventorsQuinn P. Peterson, Felicia J. Pagliuca, Douglas A. Melton, Jeffrey R. Millman, Michael Saris Segel, Mads Gurtler
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Abstract
Disclosed herein are methods, compositions, kits, and agents useful for inducing β cell maturation, and isolated populations of SC-β cells for use in various applications, such as cell therapy.
Claims24
An in vitro composition that comprises a protein kinase inhibitor, a retinoic acid signaling pathway activator, a sonic hedgehog pathway inhibitor, a TGF-beta pathway inhibitor, and a plurality of non-native human pancreatic progenitor cells that express PDX1 and NKX6.1.
An in vitro composition that comprises
- a protein kinase inhibitor comprises staurosporine;
- Ro-31-8220;
- a bisindolylmaleimide (Bis);
- 10′-{5″-[(methoxycarbonyl)amino]-2″methyl}-phenylaminocarbonylstaurosporine;
- a staralog;
- a pseudohypericin;
- or indirubin-3-monoxime, 5-Iodo;
- a TGF-beta pathway inhibitor comprising Alk5 inhibitor II;
- a BMP signaling pathway inhibitor comprising LDN193189;
- and
- a plurality of non-native human pancreatic insulin-expressing cells.
A method of in vitro cell differentiation, comprising:
- contacting an in vitro population of human pancreatic progenitor cells that express PDX1 and NKX6.1 with a retinoic acid signaling pathway activator, a sonic hedgehog pathway inhibitor, a TGF-beta pathway inhibitor, and a protein kinase inhibitor,
- wherein the method results in a plurality of the pancreatic progenitor cells in the population to differentiate into insulin-expressing cells.
Dependencies are inferred from the claim text.