Progenitor cells and methods and uses related thereto

• US 6,610,535 B1
• Filed: 11/28/2000
• Issued: 08/26/2003
• Est. Priority Date: 02/10/2000
• Status: Expired due to Term

• Current Assignee: ES Cell International Pte Ltd. (Lineage Cell Therapeutics, Inc.)
• Original Assignee: ES Cell International Pte Ltd. (Lineage Cell Therapeutics, Inc.)
• Inventors: Pang, Kevin, Lu, Kuanghui, Rubin, Lee
• Primary Examiner(s): Guzo, David
• Assistant Examiner(s): Lambertson, David A.
• Application Number:
  US09/724,632
• Time in Patent Office: 1,001 Days
• Field of Search: 435/325, 435/363, 435/366, 435/372.2, 435/375, 435/377, 435/384, 435/387, 435/391, 435/392
• US Class Current: 435/325
• 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: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: C12N 2500/02 Atmosphere, e.g. low oxygen conditions
• CPC Class Codes: C12N 2500/34 Sugars
• CPC Class Codes: C12N 2500/36 Lipids
• CPC Class Codes: C12N 2501/01 Modulators of cAMP or cGMP, e.g. non-hydrolysable analogs, phosphodiesterase inhibitors, cholera toxin
• CPC Class Codes: C12N 2501/105 Insulin-like growth factors [IGF]
• CPC Class Codes: C12N 2501/11 Epidermal growth factor [EGF]
• CPC Class Codes: C12N 2501/115 Basic fibroblast growth factor (bFGF, FGF-2)
• CPC Class Codes: C12N 2501/12 Hepatocyte growth factor [HGF]
• CPC Class Codes: C12N 2501/125 Stem cell factor [SCF], c-kit ligand [KL]
• CPC Class Codes: C12N 2501/148 Transforming growth factor alpha [TGF-a]
• CPC Class Codes: C12N 2501/23 Interleukins [IL]
• CPC Class Codes: C12N 2501/26 Flt-3 ligand (CD135L, flk-2 ligand)
• CPC Class Codes: C12N 2501/35 Vasoactive intestinal peptide [VIP]; Pituitary adenylate cyclase activating polypeptide [PACAP]
• CPC Class Codes: C12N 2501/39 Steroid hormones
• CPC Class Codes: C12N 2501/835 Neuropeptide Y [NPY]; Peptide YY [PYY]
• CPC Class Codes: C12N 2510/02 Cells for production
• CPC Class Codes: C12N 5/0647 Haematopoietic stem cells; Uncommitted or multipotent progenitors
• CPC Class Codes: C12N 5/0676 Pancreatic 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 pancreatic 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 obtaining differentiated pancreatic cell types comprising:

obtaining a cell suspension from an animal tissue;

treating the cell suspension with a growth factor preparation;

allowing proliferation of progenitor cells, which progenitor cells are propogated as non-adherent cells; and

contacting said proliferated progenitor cells with a differentiation medium and an adherent matrix,

wherein said progenitor cells adhere to said matrix and give rise to at least one differentiated pancreatic cell type.

2. The method of claim 1, wherein said animal tissue is pancreatic ductal tissue.

3. The method of claim 1, wherein said animal tissue is post-natal human tissue.

4. The method of claim 1, wherein said growth factor preparation comprises one or more of the following:

epidermal growth factor, basic fibroblast growth factor, hepatocyte growth factor, transforming growth factor alpha, insulin-like growth factor I and insulin-like growth factor II.

5. The method of claim 1, wherein said differentiated pancreatic cell type is an exocrine cell type.

6. The method of claim 1, wherein said differential pancreatic cell type is an endocrine cell type.

7. The method of claim 1, wherein said differentiation medium comprises a cAMP elevating agent and a PYY polypeptide.

8. A method of claim 1 wherein said adherent matrix is derived from a cancerous cell line.

9. The method of claim 5, wherein said exocrine cell type expresses carboxypeptidase A.

10. The method of claim 6, wherein said endocrine cell is selected from glucagon-expressing cells, insulin-expressing cells and somatostatin expressing cells.

11. The method of claim 10, wherein said insulin-expressing cells produce insulin in a glucose-regulated manner.

12. The method of claim 7, wherein said differentiation medium comprises froskolin and PYY.

13. A method of claim 8 wherein said adherent matrix is derived from a sarcoma or a bladder carcinoma.

14. A method for obtaining differentiated pancreatic cell types comprising contacting a pancreatic progenitor cell with an adherent matrix and a differentiation medium comprising a cAMP elevating agent and a PYY polypeptide, wherein said progenitor cell gives rise to at least one differentiated pancreatic cell type.

15. A method of claim 14, wherein said pancreatic progenitor cell is obtained as a nonadherent cell.

16. A method of claim 14, wherein said differentiation medium comprises forskolin and PYY.