Method of isolating bile duct progenitor cells

• US 20050208653A1
• Filed: 05/10/2005
• Published: 09/22/2005
• Est. Priority Date: 06/07/1995
• Status: Abandoned Application

• Current Assignee: ES Cell International Pte Ltd. (Lineage Cell Therapeutics, Inc.)
• Original Assignee: ES Cell International Pte Ltd. (Lineage Cell Therapeutics, Inc.)
• Inventors: Homa, Monica, Pang, Kevin
• Application Number:
  US11/125,577
• Publication Number:
  US 20050208653A1
• Time in Patent Office: Days
• US Class Current: 435/366
• CPC Class Codes: A61K 35/39 Pancreas; Islets of Langerhans Langerhans cells of epidermis A61K35/36
• CPC Class Codes: A61K 35/407 Liver; Hepatocytes
• CPC Class Codes: A61K 35/413 Gall bladder; Bile
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/20 for DNA viruses
• CPC Class Codes: C12N 2501/11 Epidermal growth factor [EGF]
• CPC Class Codes: C12N 2501/113 Acidic fibroblast growth factor (aFGF, FGF-1)
• CPC Class Codes: C12N 2501/115 Basic fibroblast growth factor (bFGF, FGF-2)
• CPC Class Codes: C12N 2501/148 Transforming growth factor alpha [TGF-a]
• CPC Class Codes: C12N 5/0672 Stem cells; Progenitor cells; Precursor cells; Oval cells
• CPC Class Codes: C12N 5/0678 Stem cells; Progenitor cells; Precursor cells

Abstract

The present invention relates to a substantially pure population of viable bile duct progenitor cells, and methods for isolating such cells. The present invention further concerns certain therapeutic uses for such progenitor cells, and their progeny.

Claims

1. (canceled)

2. A cellular composition comprising, as the cellular component, a substantially pure population of viable pancreatic progenitor cells, which progenitor cells are capable of proliferation in a culture medium and differentiate to pancreatic lineages.

3. The composition of claim 2, wherein at least 80% of the viable cells in the composition are progenitor cells.

4. The composition of claim 2, which progenitor cells are from a mammal.

5. The composition of claim 4, which mammal is a transgenic mammal.

6. The composition of claim 4, which mammal is a primate.

7. The composition of claim 6, which mammal is a human.

8. The composition of claim 4, which mammal is a miniature swine.

14. The composition of claim 2, wherein the progenitor cells express one or more of STF-1;

a PAX gene;

PTF-1;

hXBP-1;

an HNF gene;

villin;

tyrosine hydroxylase;

insulin;

glucagon;

or neuropeptide Y.

15. The composition of claim 14, wherein the progenitor cells express STF-1 and PAX6.

20. The composition of claim 2, which progenitor cells can be maintained in culture for at least about 7 days.

37. A pharmaceutical composition comprising the cellular composition of claim 2.

9-13. -13. (canceled)

16-19. -19. (canceled)

21. (canceled)

22. A cellular composition consisting essentially of, as the cellular population, viable pancreatic progenitor cells capable of self-regeneration in a culture medium, which progenitor cells differentiate to members of the pancreatic lineage.

23. The composition of claim 22, which progenitor cells are isolated from a hepatic duct tissue, or are the progeny thereof.

24. The composition of claim 22, which progenitor cells are isolated from cystic duct tissue, or are the progeny thereof.

25. The composition of claim 22, which progenitor cells are isolated from pancreatic duct tissue, or are the progeny thereof.

26. The composition of claim 22, which progenitor cells are isolated from common bile duct tissue, or are the progeny thereof.

27. The composition of claim 22, which progenitor cells are responsive to one or more growth factor selected from a group consisting of IGF, EGF, TGF, FGF, HGF and VEGF, or orthologous or paralogous factors thereof.

39. A pharmaceutical composition comprising the cellular composition of claim 22.

28. A cellular composition comprising pancreatic progenitor cells, wherein the progenitor cells are at least 80% pure, are capable of self-regeneration in a culture medium and differentiate to pancreatic lineages.

29. The composition of claim 28, which progenitor cells are inducible to differentiate into pancreatic islet cells.

30. The composition of claim 29, which islet cells are pancreatic β

islet cells.

31. The composition of claim 29, which islet cells are pancreatic α

islet cells.

32. The composition of claim 29, which islet cells are pancreatic δ

islet cells.

33. The composition of claim 29, which islet cells are pancreatic φ

islet cells.

34. The composition of claim 28, wherein the progenitor cells are characterized by expression of STF-1 and PAX6.

40. A pharmaceutical composition comprising the cellular composition of claim 28.

41-54. -54. (canceled)

55. A method for treating a disorder characterized by insufficient insulin activity, in a subject, comprising introducing into the subject a pharmaceutical composition including a substantially pure population of pancreatic progenitor cells and a pharmaceutically acceptable carrier.

56. The method of claim 55, wherein the subject is a human.

57. The method of claim 55, wherein the disorder is an insulin dependent diabetes.

58. The method of claim 57, wherein the insulin dependent diabetes is type I diabetes.

59. The method of claim 55, wherein the pancreatic progenitor cells are induced to differentiate into pancreatic islet cells in the subject.

60. The method of claim 55, wherein the pancreatic progenitor cells are induced to differentiate into pancreatic β

islet cells in culture prior to introduction into the subject.

61. The method of claim 55, wherein the pancreatic progenitor cells are characterized by expression of STF-1 and PAX6.

62. A method for treating a disorder characterized by insufficient liver function, in a subject, comprising introducing into the subject a pharmaceutical composition including hepatic progenitor cells and a pharmaceutically acceptable carrier.

63. The method of claim 62, wherein the subject is a human.

64. The method of claim 62, wherein the disorder is selected from the group consisting of cirrhosis, hepatitis B, hepatitis C, sepsis or ELAD.

65. The method of claim 62, wherein the hepatic progenitor cells are induced to differentiate into hepatocytes in the subject.

66. The method of claim 62, wherein the hepatic progenitor cells are induced to differentiate into hepatocytes in culture prior to introduction into the subject.

67. The method of claim 62, wherein the hepatic progenitor cells express HNF3, alphafetoprotein (AFP), albumin, and ATBF-1, and differentiate into hepatocytes.