Methods of treating disease using sertoli cells an allografts or xenografts

• US 5,725,854 A
• Filed: 04/13/1995
• Issued: 03/10/1998
• Est. Priority Date: 04/13/1994
• Status: Expired due to Term

• Current Assignee: Research Corporation Technologies
• Original Assignee: Research Corporation Technologies
• Inventors: Selawry, Helena P.
• Primary Examiner(s): Wityshyn, Michael G.
• Assistant Examiner(s): Ware, Deborah
• Application Number:
  US08/421,641
• Time in Patent Office: 1,062 Days
• Field of Search: 424/93.7, 435/240.1
• US Class Current: 424/93.7
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 35/39 Pancreas; Islets of Langerhans Langerhans cells of epidermis A61K35/36
• CPC Class Codes: A61K 35/48 Reproductive organs
• CPC Class Codes: A61K 38/13 Cyclosporins
• CPC Class Codes: A61K 38/28 Insulins
• 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: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/08 for glucose homeostasis pancreatic hormones A61P5/48
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: C12N 2502/246 Cells of the male genital tract, non-germinal testis cells
• CPC Class Codes: C12N 2510/00 Genetically modified cells
• CPC Class Codes: C12N 2510/04 Immortalised cells
• CPC Class Codes: C12N 5/0676 Pancreatic cells
• CPC Class Codes: C12N 5/0677 Three-dimensional culture, tissue culture or organ culture; Encapsulated cells
• CPC Class Codes: C12N 5/0683 Cells of the male genital tract, e.g. prostate, epididymis; Non-germinal cells from testis, e.g. Leydig cells, Sertoli cells spermatogonia C12N5/061
• CPC Class Codes: Y10S 435/975 Kit

Abstract

The present invention describes a method of treating a disease that results from a deficiency of a biological factor which includes administering to a mammal Sertoli cells and cells that produce the biological factor. In particular, the present invention describes a method of treating diabetes mellitus by transplanting pancreatic islet of Langerhans cells in conjunction with Sertoli cells to create an immunologically privileged site. A method of creating an immunologically privileged site in a mammal for cellular transplants is further described by the present invention. A pharmaceutical composition comprising Sertoli cells and cells that produce a biological factor is also provided.

Claims

1. A method of treating a disease that results from a deficiency of a biological factor in a mammal wherein said method comprises administering Sertoli cells and a therapeutically effective amount of cells that produce said biological factor to a mammal in need of such treatment, wherein said Sertoli cells are administered in an amount effective to create an immunologically privileged site.

2. The method of claim 1 wherein said mammal is a human.

3. The method of claim 1 wherein said biological factor is a hormone.

4. The method of claim 1 wherein said biological factor is insulin and said disease is diabetes mellitus.

5. The method of claim 4 wherein said cells that produce said biological factor are pancreatic islet of Langerhans cells.

6. The method of claim 1 wherein said cells that produce said biological factor are cells transformed by a nucleic acid encoding said biological factor.

7. The method of claim 1 wherein said administering is by transplantation.

8. The method of claim 7 wherein said transplantation is by xenograft.

9. The method of claim 7 wherein said transplantation is by allograft.

10. The method of claim 1 wherein said Sertoli cells are administered in a dosage ranging from 10⁵ to 10¹⁰ cells.

11. The method of claim 1 wherein said cells that produce said biological factor are administered in a dosage of from 10⁵ to 10¹⁰ cells.

12. The method of claim 1 which further comprises administering an immunosuppressive agent.

13. The method of claim 12 wherein said immunosuppressive agent is administered for a time sufficient to permit said transplanted cells to be functional.

14. The method of claim 12 wherein said immunosuppressive agent is cyclosporine.

15. The method of claim 14 wherein said cyclosporine is administered at a dosage of from 5 to 40 mg/kg body wt.

16. The method of claim 1 which further comprises administering a therapeutically effective amount of exogenous biological factor following the transplantation of said cells that produce said biological factor.

17. The method of claim 1 wherein said cells that produce said biological factor are co-cultured with Sertoli cells in tissue culture.

18. The method of claim 17 wherein said cells that produce said biological factor are cryopreserved prior to co-culturing with Sertoli cells in tissue culture.

19. A method of treating diabetes mellitus in a mammal wherein said method comprises administering to a diabetic mammal Sertoli cells in an amount effective to create an immunologically privileged site and a therapeutically effective amount of pancreatic islet of Langerhans cells for release of insulin.

20. The method of claim 19 wherein said diabetes mellitus is type I or type II.

21. The method of claim 19 wherein said mammal is a human.

22. The method of claim 19 wherein said Sertoli cells are human, bovine or porcine.

23. The method of claim 19 wherein said pancreatic islet of Langerhans cells are human, bovine or porcine.

24. The method of claim 19 wherein said administering is by transplantation.

25. The method of claim 24 wherein said transplantation is by injection into the renal subcapsular space.

26. The method of claim 24 wherein said transplantation is by subcutaneous injection.

27. The method of claim 19 wherein said Sertoli cells are administered at a dosage ranging from 10⁵ to 10¹⁰ cells.

28. The method of claim 19 wherein said islet of Langerhans cells are administered at a dosage ranging from 5-1000 islet cells/g body wt.

29. The method of claim 19 which further comprises the administration of an effective amount of an immunosuppressive agent.

30. The method of claim 29 wherein said immunosuppressive agent is administered to maintain the release of insulin from the eyelet cells.

31. The method of claim 29 wherein said immunosuppressive agent is cyclosporine.

32. The method of claim 31 wherein said cyclosporine is administered at a dosage of 5 to 40 mg/kg body wt.

33. The method of claim 19 which further comprises administering a therapeutically effective amount of insulin following transplantation of said pancreatic islet of Langerhans cells.

34. A method of creating an immunologically privileged site in a mammal wherein said method comprises transplanting isolated Sertoli cells into a mammal.

35. The method of claim 34 wherein said mammal is a human.

36. The method of claim 34 wherein said Sertoli cells are injected into a renal subcapsular space.

37. The method of claim 34 wherein said Sertoli cells are subcutaneously injected into the mammal.

38. The method of claim 34 wherein said Sertoli cells are transplanted at a dosage ranging from 10⁵ to 10¹⁰ cells.

39. The method of claim 34 wherein said Sertoli cells are human, bovine or porcine.

40. A method of increasing the recovery and proliferation of biological factor producing cells ex vivo comprising co-culturing said cells with Sertoli cells under conditions sufficient to achieve said increased recovery and proliferation.