Endocrine pancreas differentiation of adipose tissue-derived stromal cells and uses thereof

• US 20030124721A1
• Filed: 11/12/2002
• Published: 07/03/2003
• Est. Priority Date: 11/09/2001
• Status: Abandoned Application

• Current Assignee: Artecel Inc.
• Original Assignee: Artecel Inc.
• Inventors: Gimble, Jeffrey M., Halvorsen, Yuan-Di C., Cheatham, Bentley
• Application Number:
  US10/293,398
• Publication Number:
  US 20030124721A1
• Time in Patent Office: Days
• US Class Current: 435/366
• CPC Class Codes: A61K 2035/126 Immunoprotecting barriers, e.g. jackets, diffusion chambers
• 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 1/18 for pancreatic disorders, e.g. pancreatic enzymes
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 5/48 of the pancreatic hormones
• CPC Class Codes: A61P 5/50 for increasing or potentiating the activity of insulin
• CPC Class Codes: C12N 2501/115 Basic fibroblast growth factor (bFGF, FGF-2)
• CPC Class Codes: C12N 2502/1305 Adipocytes
• CPC Class Codes: C12N 2506/1384 from adipose-derived stem cells [ADSC], from adipose stromal stem cells
• CPC Class Codes: C12N 2510/00 Genetically modified cells
• CPC Class Codes: C12N 5/0676 Pancreatic cells

Abstract

The invention provides cells, compositions and methods based on the differentiation of adipose tissue-derived stromal cells into a cell expressing at least one genotypic or phenotypic characteristic of a pancreas cell. The cells produced in the method are useful in providing a source of differentiated and functional cells for research, implantation, transplantation and development of tissue engineered products for the treatment of diseases of the pancreas and pancreatic tissue repair.

Claims

1. An isolated adipose tissue-derived stromal cell induced to express at least one characteristic of endocrine pancreas-derived cell.

2. The cell of claim 1, wherein the cell is induced to differentiate in vitro.

3. The cell of claim 1, wherein the cell is induced to differentiate in vivo.

4. The cell of claim 1, wherein exogenous genetic material has been introduced into the cell.

5. The cell of claim 1, wherein the cell is human.

6. The cell of claim 1, wherein the cell secretes a hormone.

7. The cell of claim 6, wherein the hormone is selected from the group of hormones consisting of insulin, glucagon, somatostatin, or pancreatic polypeptide

8. The cell of claim 7, wherein the hormone is insulin

14. An implant comprising the cells of any of claims 1-8.

15. The implant of claim 14 further comprising a biocompatible polymer.

16. The implant of claim 15, wherein the biocompatible polymer is a hydrogel.

17. The implant of claim 15, wherein the biocompatible polymer is collagen-derived, polyglycolic acid, polylactic acid, polyglycolic/polylactic acid, hyaluronate or fibrin.

18. A method of producing hormones, comprising (a) culturing the cell of any of claims 1-8 within a medium under conditions sufficient for the cell to secrete the hormone into the medium and (b) isolating the hormone from the medium.

19. The method of claim 18, wherein the hormone produced is selected from the group consisting of insulin, glucagon, somatostatin or pancreatic polypeptide.

20. The method of claim 19, wherein the hormone produced is insulin.

24. The cell of claim 1 further encapsulated in a biomaterial compatible with transplantation into a host.

25. The cell of claim 24, wherein the encapsulation material is selected from the group consisting of collagen derivatives, hydrogels, calcium alginate, agarose, hyaluronic acid, poly-lactic acid/poly-glycolic acid derivatives and fibrin.

26. The use of the cell of any of claims 1-8, or 21-25 implanted into a host.

27. The use of the implant of any of claim 14-17 engrafted into a host.

9. A method for differentiating isolated adipose tissue-derived stromal cells to display at least one endocrine pancreas cell marker comprising contacting an isolated adipose tissue-derived stromal cell with an endocrine pancreas inducing substance.

10. The method of claim 9, wherein the endocrine pancreas inducing substance is in a chemically defined cell culture medium.

11. A method of treating a pancreatic endocrine disorder or degenerative condition in a host comprising:

i) inducing isolated adipose tissue-derived stromal cells to express at least one endocrine pancreas cell marker; and

ii) transplanting the induced cells into the host.

12. The method of claim 11, wherein the adipose tissue-derived stromal cells are isolated from the host.

13. The method of claim 11, wherein the pancreatic endocrine disorder or degenerative condition is Type I Diabetes Mellitus, Type II Diabetes Mellitus, lipodystrophy associated disease, a chemically-induced disease, a pancreatitis-associated disease, or a trauma-associated disease.

21. An isolated adipose tissue-derived stromal cell which is dedifferentiated in vitro and then induced to express at least one characteristic of an endocrine pancreas cell.

22. The dedifferentiated cell of claim 21 induced in vivo to express at least one characteristic of an endocrine pancreas cell.

23. An isolated adipose tissue-derived cell induced in culture to express at least one characteristic of an endocrine pancreas cell, wherein the induced cell is:

a) disaggregated and transferred to suspended cell cultures;

b) the suspended cell cultures are grown until evidence of islet cell cluster formation is observed; and

, wherein

c) the resulting islet cell clusters are engrafted into a host.