CD56 positive human adult pancreatic endocrine progenitor cells

• US 9,068,169 B2
• Filed: 05/02/2008
• Issued: 06/30/2015
• Est. Priority Date: 09/06/2002
• Status: Active Grant

• Current Assignee: ReNeuron Limited (ReNeuron Group Plc)
• Original Assignee: ReNeuron Limited (ReNeuron Group Plc)
• Inventors: Tsang, Wen-Ghih, Zheng, Tianli, Liu, Wei
• Primary Examiner(s): DAVIS, RUTH A
• Application Number:
  US12/114,604
• Publication Number:
  US 20090246178A1
• Time in Patent Office: 2,615 Days
• Field of Search: 435/378, 435/370, 435/373, 435/375, 435/384
• US Class Current: 1/1
• 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 obtaining a culture of propagating pancreatic cells that exhibit a CD56 protein as a cell surface marker comprising:

(a) isolating a population of cells from a pancreas that include undifferentiated pancreatic cells and differentiated pancreatic cells;

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

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

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

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 propagating pancreatic cell culture is differentiated into an aggregate of insulin producing pancreatic cells.

11. The method of claim 10, wherein the step of differentiating the cells comprises culturing the cells on plates coated with collagen IV.

12. The method of claim 10, wherein the step of differentiating the cells comprises culturing the cells in a media comprising a differentiation factor.

13. The method of claim 12, wherein the differentiation factor is selected from the group consisting of hepatocyte growth factor, keratinocyte growth factor, and exendin-4.

14. The method of claim 13, wherein the differentiation factor is hepatocyte growth factor.