Compositions and Methods for Altering Pancreas or Liver Function

• US 20100129351A1
• Filed: 04/18/2008
• Published: 05/27/2010
• Est. Priority Date: 05/03/2007
• Status: Active Grant

• Current Assignee: The Institute for Cancer Research (Fox Chase Cancer Center)
• Original Assignee: The Institute for Cancer Research (Fox Chase Cancer Center)
• Inventors: Kashima, Yasushige, Zaret, Kenneth S.
• Granted Patent: US 8,329,467 B2
• Time in Patent Office: Days
• US Class Current: 424/130.100
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 1/18 for pancreatic disorders, e.g. pancreatic enzymes
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: C12N 2501/58 Adhesion molecules, e.g. ICAM, VCAM, CD18 (ligand), CD11 (ligand), CD49 (ligand)
• CPC Class Codes: C12N 2501/998 Proteins not provided for elsewhere
• CPC Class Codes: C12N 5/0676 Pancreatic cells

Abstract

Methods for altering pancreatic and liver cell function are provided, wherein the compositions and methods are based on use of netrin-4 or on altering the activity of netrin-4.

Claims

1. A method for inducing differentiation of an endodermal cell or a progenitor cell into a pancreatic cell or a liver cell comprising contacting an endodermal cell or a progenitor cell with an effective amount of netrin-4 thereby inducing differentiation of the endodermal cell or the progenitor cell into a pancreatic cell or a liver cell.

2. The method of claim 1 wherein said cell is a partially differentiated liver or pancreatic progenitor cell.

9. A composition comprising an isolated pancreatic or liver cell differentiated by the method of claim 1.

10. A pharmaceutical composition comprising isolated pancreatic or liver cells differentiated by the method of claim 1 and a pharmaceutically acceptable vehicle.

3. A method for altering pancreatic or liver cell function comprising contacting a pancreatic or liver cell with an effective amount of netrin-4, wherein contact of the cell with netrin-4 results in an alteration in the function of the pancreatic or liver cell.

4. A method for altering pancreatic or liver cell function comprising contacting a pancreatic or liver cell with an effective amount of a composition comprising a netrin-4 protein, a netrin-4 antibody, a netrin-4 mimetic, a netrin-4 agonist, a netrin-4 antagonist, a mutated netrin-4 protein, or a netrin-4 variant or fragment thereof, formulated in a pharmaceutically acceptable vehicle, wherein contact of the cell with said composition results in an alteration in the function of the pancreatic or liver cell.

6. The method of claim 4 wherein said disease is diabetes mellitus.

5. A method for preventing or treating a disease of the pancreas or liver in a patient comprising administering to a patient a therapeutically effective amount of a composition comprising netrin-4 formulated in a pharmaceutically acceptable vehicle, wherein administration of said composition results in prevention or treatment of a disease of the pancreas or liver.

7. A method for preventing or treating a disease of the pancreas or liver in a patient comprising administering to a patient a therapeutically effective amount of a composition comprising a netrin-4 protein, netrin-4 antibody, a netrin-4 mimetic, a netrin-4 agonist, a netrin-antagonist, a mutated netrin-4 protein, or a netrin-4 variant or fragment thereof, formulated in a pharmaceutically acceptable vehicle, wherein administration of the composition results in prevention or treatment of a disease of the pancreas or liver.

8. A method of restoring function of a damaged pancreatic or liver tissue comprising contacting a damaged pancreas or liver tissue with an effective amount of netrin-4, wherein contact of the damaged tissue with netrin-4 results in a restoration of function of the damaged tissue.