Method of isolating bile duct progenitor cells

• US 5,861,313 A
• Filed: 06/07/1995
• Issued: 01/19/1999
• Est. Priority Date: 06/07/1995
• Status: Expired due to Term

• Current Assignee: ES Cell International Pte Ltd. (Lineage Cell Therapeutics, Inc.)
• Original Assignee: Ontogeny, Inc. (Curis, Inc.)
• Inventors: Pang, Kevin K., Homa, Monica W.
• Primary Examiner(s): Witz, Jean C.
• Application Number:
  US08/478,064
• Time in Patent Office: 1,322 Days
• Field of Search: 435/347, 435/370, 435/373, 435/384, 435/387, 435/392, 424/93.21
• US Class Current: 435/347
• 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. A method for isolating progenitor cells from a bile duct comprising

culturing a bile duct explant comprising both an epithelial layer and a stromal layer, which explant retains in culture the original epithelial-mesenchymal microarchitecture of a mammalian bile duct, wherein said explant is maintainable in culture for at least twenty-four hours, and wherein said explant includes at least on progenitor cell which has the ability to proliferate;

contacting said explant with an agent which causes proliferation of progenitor cells in said explant; and

isolating from said explant progenitor cells that proliferate in response to said agent.

2. The method of claim 1, wherein said agent is a growth factor.

3. The method of claim 2, wherein said growth factor is selected from a group consisting of IGF, EGF, TGF, FGF, HGF, VEGF, and orthologous or paralogous factors thereof.

4. The method of claim 1, wherein said progenitor cells are pancreatic progenitor cells.

5. The method of claim 1, wherein said progenitor cells are hepatic progenitor cells.

6. The method of claim 1, wherein said explant is cultured in medium deficient in biological extracts.

7. The method of claim 1, wherein said medium is deficient in serum.

8. The method of claim 1, wherein said bile duct is a common bile duct.

9. The method of claim 1, wherein said isolated progenitor cells have fewer than 20% of lineage committed cells.

10. The method of claim 1, wherein said explant is from a mammal.

11. The method of claim 10, which mammal is a transgenic mammal.

12. The method of claim 10, which mammal is a primate.

13. The method of claim 12, which mammal is a human.

14. The method of claim 11, which mammal is a miniature swine.

15. The method of claim 4, wherein the progenitor cells express one or more of IPF-1, insulin, amylase, glucagon, and somatostatin.

16. The method of claim 4, wherein the progenitor cells are inducible to differentiate into pancreatic islet cells, e.g., β

islet cells, α

islet cells, δ

islet cells, or φ

islet cells.