Stem cell differentiation

• US 20030032183A1
• Filed: 05/23/2002
• Published: 02/13/2003
• Est. Priority Date: 05/25/2001
• Status: Abandoned Application

• Current Assignee: CyThera, Inc. (Vertex Pharmaceuticals Incorporated)
• Original Assignee: CyThera, Inc. (Vertex Pharmaceuticals Incorporated)
• Inventors: Sheridan, Steven D.
• Application Number:
  US10/156,602
• Publication Number:
  US 20030032183A1
• Time in Patent Office: Days
• US Class Current: 435/370
• CPC Class Codes: A61K 35/12 Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells vaccines or medicinal preparations containing antigens or antibodies A61K39/00
• 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: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C12N 2501/335 Glucagon; Glucagon-like peptide [GLP]; Exendin
• CPC Class Codes: C12N 2501/345 Gastrin; Cholecystokinins [CCK]
• CPC Class Codes: C12N 2501/385 of the family of the retinoic acid recptor, e.g. RAR, RXR; Peroxisome proliferator-activated receptor [PPAR]
• CPC Class Codes: C12N 2506/02 from embryonic cells
• CPC Class Codes: C12N 5/067 Hepatocytes
• CPC Class Codes: C12N 5/0676 Pancreatic cells

Abstract

Treatment of stem cells with a retinoid induces differentiation of the stem cells into hepaticopancreatic tissue.

Claims

1. A method of inducing stem cell differentiation, comprising treating isolated stem cells with a retinoid under conditions effective to cause at least a portion of the stem cells to differentiate into hepaticopancreatic tissue.

2. The method of claim 1 wherein the stem cells are obtained from a stem cell source selected from the group consisting of placenta, bone marrow, adipose tissue, neural tissue, umbilical cord, blastocyst inner cell mass, and germ cells.

3. The method of claim 1 wherein the stem cells are mammalian embryonic stem cells.

4. The method of claim 1 wherein the retinoid is vitamin A.

5. The method of claim 1 wherein the retinoid is selected from the group consisting of retinol, retinal and retinoic acid.

6. The method of claim 1 wherein the retinoid is retinoic acid.

7. The method of claim 1 wherein the hepaticopancreatic tissue is pancreatic tissue.

8. The method of claim 1 wherein the hepaticopancreatic tissue is pancreatic endocrine tissue.

9. The method of claim 8 wherein the hepaticopancreatic tissue comprises insulin-producing cells.

10. The method of claim 9 wherein the insulin-producing cells are glucose-responsive.

11. The method of claim 1 wherein the hepaticopancreatic tissue is liver tissue.

12. The method of claim 1 wherein the conditions are effective to differentiate at least about 1% of the stem cells into hepaticopancreatic tissue.

13. The method of claim 1 wherein the conditions are effective to differentiate at least about 5% of the stem cells into hepaticopancreatic tissue.

14. The method of claim 1 further comprising treating the isolated stem cells with a morphogen.

15. The method of claim 14 wherein the morphogen is selected from the group consisting of a member of the glucagon-like peptide family, a cAMP raising agent, nicotinamide, a transcription factor, a protein growth factor, and mixtures thereof.

16. The method of claim 15 wherein the morphogen is selected from the group consisting of GLP-1, exendin-4, PDX-1, Ngn-3, gastrin, gastrin-releasing peptide, hepatocyte growth factor, betacellulin, and mixtures thereof.

17. A composition comprising the hepaticopancreatic tissue produced by the method of claim 1.

18. The composition of claim 17 wherein the hepaticopancreatic tissue comprises glucose-responsive insulin-producing cells.

19. The composition of claim 17 comprising about 1% or more of the hepaticopancreatic tissue produced by the method of claim 1.

20. The composition of claim 17 comprising about 10% or more of the hepaticopancreatic tissue produced by the method of claim 1.

21. The composition of claim 20 made by purifying the composition of claim 17.

22. A method of treatment comprising identifying a mammal having an extraintestinal gastrointestinal disorder and administering to the mammal a therapeutically effective amount of the composition of claim 17.

23. The method of claim 22 wherein the extraintestinal gastrointestinal disorder is a hepaticopancreatic disorder.

24. The method of claim 23 wherein the hepaticopancreatic disorder is selected from the group consisting of diabetes, pancreatitis, hepatic cirrhosis, hepatitis, cancer and pancreatico-biliary disease.

25. The method as claimed in claim 23 wherein the hepaticopancreatic disorder is diabetes.

26. The method as claimed in claim 25 wherein the mammal is a human.

27. The method as claimed in claim 26 wherein the hepaticopancreatic tissue comprises glucose-responsive insulin-producing cells.

28. A method of treatment comprising identifying a human having diabetes and administering to the human a therapeutically effective amount of the composition of claim 18.