CD56 POSITIVE HUMAN ADULT PANCREATIC ENDOCRINE PROGENITOR CELLS

• US 20090246178A1
• Filed: 05/02/2008
• Published: 10/01/2009
• Est. Priority Date: 09/06/2002
• Status: Active Grant

• Current Assignee: ReNeuron Limited (ReNeuron Group Plc)
• Original Assignee: ReNeuron Limited (ReNeuron Group Plc)
• Inventors: LIU, WEI, TSANG, WEN-GHIH, ZHENG, TIANLI
• Granted Patent: US 9,068,169 B2
• Time in Patent Office: Days
• US Class Current: 424/93.700
• 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 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: C12N 2500/34 Sugars
• CPC Class Codes: C12N 2501/117 Keratinocyte growth factors (KGF-1, i.e. FGF-7; KGF-2, i.e. FGF-12)
• CPC Class Codes: C12N 2501/12 Hepatocyte growth factor [HGF]
• CPC Class Codes: C12N 2501/599 with CD designations not provided for elsewhere
• CPC Class Codes: C12N 2533/54 Collagen; Gelatin
• CPC Class Codes: C12N 5/0678 Stem cells; Progenitor cells; Precursor cells

Abstract

The invention relates to the discovery of a selective cell surface marker that permits the selection of a unique subset of pancreatic stems cells having a high propensity to differentiate into insulin producing cells or into insulin producing cell aggregates.

Claims

1. A method of providing pancreatic endocrine function to a mammal in need of such function, the method comprising the steps of:

(a) isolating pancreatic cells from a pancreas;

(b) contacting the pancreatic cells with a CD56 binding reagent;

(c) selecting undifferentiated pancreatic cells that specifically bind to the CD56 binding reagent, wherein the undifferentiated pancreatic cells can be expanded in culture;

(d) separating the selected, undifferentiated pancreatic cells from pancreatic cells that do not bind the CD56 binding reagent to obtain a culture of propagating pancreatic cells that exhibit the CD56 protein as a cell surface marker; and

(e) implanting into the mammal the propagating pancreatic cells in an amount sufficient to produce a measurable amount of insulin in the mammal.

2. The method of claim 1, wherein the CD56 binding reagent is labeled.

3. The method of claim 1, wherein the step of selecting is done by fluorescence activated cell sorting.

4. The method of claim 1, wherein the CD56 binding reagent is an antibody that specifically binds to the CD56 protein.

5. The method of claim 1, wherein the CD56 binding reagent is an antibody that specifically binds to an oligosaccharide linked to the CD56 protein.

6. The method of claim 1, wherein the CD56 binding reagent is a lectin that specifically binds to an oligosaccharide linked to the CD56 protein.

7. The method of claim 1, wherein the CD56 binding reagent is a ligand of the CD56 protein.

8. The method of claim 7, wherein the ligand is selected from the group consisting of soluble CD56, heparin, and heparin sulfate.

9. The method of claim 1, wherein the pancreas is from a human.

10. The method of claim 1, wherein the mammal is a human.

11. The method of claim 1, wherein the propagating pancreatic cells differentiate into aggregates of insulin producing pancreatic cells after implantation into the mammal.

12. The method of claim 1, wherein before implantation into the mammal, the propagating pancreatic cell culture is differentiated into an aggregate of insulin producing pancreatic cells.

13. The method of claim 12, wherein the step of differentiating the cells comprises culturing the cells on plates coated with collagen IV.

14. The method of claim 12, wherein the step of differentiating the cells comprises culturing the cells in a media comprising a differentiation factor.

15. The method of claim 14, wherein the differentiation factor is selected from the group consisting of hepatocyte growth factor, keratinocyte growth factor, and exendin-4.

16. The method of claim 15, wherein the differentiation factor is hepatocyte growth factor.

17. The method of claim 12, wherein the mammal is a human.