Treatments using sertoli cells

• US 6,149,907 A
• Filed: 04/23/1999
• Issued: 11/21/2000
• 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): Naff, David M.
• Assistant Examiner(s): Ware, Deborah K.
• Application Number:
  US09/298,015
• Time in Patent Office: 578 Days
• Field of Search: 435/326, 435/347, 435/366, 435/363, 435/373, 435/374, 435/325, 424/93.7
• US Class Current: 424/93.7
• CPC Class Codes: A61K 2035/122 for inducing tolerance or supression of immune responses
• CPC Class Codes: A61K 2035/126 Immunoprotecting barriers, e.g. jackets, diffusion chambers
• CPC Class Codes: A61K 2035/128 capsules, e.g. microcapsules
• 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 35/12 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 35/39 Pancreas; Islets of Langerhans Langerhans cells of epidermis A61K35/36
• CPC Class Codes: A61K 35/48 Reproductive organs
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• 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: 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 5/0677 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

Abstract

A method of treating a disease is provided that results from a deficiency of a biological factor which comprises administering to a mammal Sertoli cells and also cells that produce the biological factor. A method of treating diabetes mellitus is carried out 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 and providing cell stimulatory factors in a mammal for transplants is also carried out. A method of co-localizing islet cells with Sertoli cells and the use of the co-localized product for treating diabetes mellitus is further provided. Further described is a method of creating systemic tolerance to foreign antigens. A method of enhancing the viability, maturation, proliferation of functional capacity of cells in tissue culture is also provided. In addition, pharmaceutical compositions comprising Sertoli cells and cells that produce a biological factor, and/or a pharmaceutically acceptable carrier are further provided.

Claims

1. A method of creating an immunologically privileged site in a mammal wherein said method comprises transplanting isolated Sertoli cells obtained from a cell line into a mammal.

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

3. The method of claim 1 wherein said Sertoli cells are injected into the renal subcapsular space.

4. The method of claim 1 wherein said Sertoli cells are injected into the subcutaneous facie.

5. The method of claim 1 wherein said Sertoli cells are transplanted at a dosage ranging from 10⁵ to 10¹⁰ cells.

6. The method of claim 5 wherein said Sertoli cells are obtained by the steps comprising:

a. isolating mammalian Sertoli cells from mammalian tissue;

b. incubating said isolated mammalian Sertoli cells with a mutagen under conditions sufficient to transform said Sertoli cells;

c. collecting said transformed Sertoli cells; and

d. optionally screening transformed Sertoli cells for expression of an appropriate isolate for cloning.

7. The method of claim 1 wherein said Sertoli-cells are human, bovine or porcine.

8. The method of claim 1 wherein said Sertoli cells are obtained by the steps comprising:

a. isolating mammalian Sertoli cells from mammalian tissue;

b. incubating said isolated mammalian Sertoli cells with virus producing cells under conditions sufficient to transform said Sertoli cells;

c. isolating said transformed Sertoli cells from the virus producing cell; and

d. optionally screening transformed Sertoli cells for expression of an appropriate isolate for cloning.

9. The method of claim 8 wherein said virus producing cells are SV40 or polyoma virus.

10. The method of claim 1 wherein said Sertoli cells are obtained by the steps comprising:

a. isolating mammalian Sertoli cells from mammalian tissue;

b. incubating said isolated mammalian Sertoli cells with a mutagen under conditions sufficient to transform said Sertoli cells;

c. collecting said transformed Sertoli cells; and

d. optionally screening transformed Sertoli cells for expression of an appropriate isolate for cloning.

11. A method of creating systemic tolerance to subsequent transplants comprising transplanting Sertoli cells prior to said subsequent transplant with a transplant in an amount sufficient to tolerize said mammal.

12. The method of claim 11 wherein said transplants are endocrine cells.

13. The method of claim 11 wherein said Sertoli cells are administered in a dosage ranging from 10⁵ to 10¹⁰ cells.

14. The method of claim 11 wherein endocrine cells are simultaneously transplanted with said Sertoli cells.

15. The method of claim 11 wherein said Sertoli cells are obtained from a cell line.

16. The method of claim 15 wherein said Sertoli cells are obtained by the steps comprising:

a. isolating mammalian Sertoli cells from mammalian tissue;

b. incubating said isolated mammalian Sertoli cells with virus producing cells under conditions sufficient to transform said Sertoli cells;

c. isolating said transformed Sertoli cells from the virus producing cell; and

d. optionally screening transformed Sertoli cells for expression of an appropriate isolate for cloning.

17. The method of claim 16 wherein said virus producing cells are SV40 or polyoma virus.

18. A method of enhancing the maturation, proliferation and functional capacity of mammalian cells in tissue culture comprising co-culturing said cells with Sertoli cells.

19. The method of claim 18 wherein said Sertoli cells are co-cultured in an amount ranging from 10⁵ to 10¹⁰ cells.

20. The method of claim 18 wherein said Sertoli cells are obtained from a cell line.

21. The method of claim 20 wherein said Sertoli cells are obtained by the steps comprising:

a. isolating mammalian Sertoli cells from mammalian tissue;

b. incubating said isolated mammalian Sertoli cells with virus producing cells under conditions sufficient to transform said Sertoli cells;

c. isolating said transformed Sertoli cells from the virus producing cell; and

d. optionally screening transformed Sertoli cells for expression of an appropriate isolate for cloning.

22. The method of claim 20 wherein said Sertoli cells are obtained by the steps comprising:

a. isolating mammalian Sertoli cells from mammalian tissue;

b. incubating said isolated mammalian Sertoli cells with a mutagen under conditions sufficient to transform said Sertoli cells;

c. collecting said transformed Sertoli cells; and

d. optionally screening transformed Sertoli cells for expression of an appropriate isolate for cloning.

23. The method of claim 18 wherein said virus producing cells are SV40 or polyoma virus.

24. The method of claim 18 wherein the mammalian cells and the Sertoli cells are co-localized.

25. The method of claim 18 wherein the mammalian cells and the Sertoli cells are co-encapsulated.

26. A method of enhancing the recovery rate and viability of frozen mammalian cells in tissue culture-comprising co-culturing said cells with Sertoli cells.

27. The method of claim 26 wherein said mammalian cells are endocrine cells or germ cells.

28. A pharmaceutical composition comprising Sertoli cells obtained from a cell line, pancreatic islet of Langerhans cells and a pharmaceutically acceptable carrier.

29. A pharmaceutical composition comprising Sertoli-cells obtained from a cell line and a pharmaceutically acceptable carrier.

30. An article of manufacture comprising a packaging material and Sertoli cells contained within said packaging material, wherein said Sertoli cells are effective for creating an immunologically privileged site in a mammal, and wherein said packaging material contains a label that indicates that said Sertoli cells can be used for creating an immunologically privileged site in a mammal.

31. A pharmaceutical composition comprising Sertoli cells obtained from a cell line, and cells that produce a biological factor and a pharmaceutically acceptable carrier.

32. The composition of claim 31 wherein said biological factor is a hormone.

33. The composition of claim 31 wherein said cells that produce a biological factor are pancreatic islet of Langerhans cells.

34. The composition of claim 31 wherein said cells that produce said biological factor are cells that are transformed by a nucleic acid encoding said biological factor.

35. The composition of claim 31 wherein said Sertoli cells are obtained by the steps comprising:

a. isolating mammalian Sertoli cells from mammalian tissue;

b. incubating said isolated mammalian Sertoli cells with virus producing cells under conditions sufficient to transform said Sertoli cells;

c. isolating said transformed Sertoli cells from the virus producing cell; and

d. optionally screening transformed Sertoli cells for expression of an appropriate isolate for cloning.

36. The composition of claim 31 wherein said Sertoli cells are obtained by the steps comprising:

a. isolating mammalian Sertoli cells from mammalian tissue;

b. incubating said isolated mammalian Sertoli cells with a mutagen under conditions sufficient to transform said Sertoli cells;

c. collecting said transformed Sertoli cells; and

d. optionally screening transformed Sertoli cells for expression of an appropriate isolate for cloning.

37. The composition of claim 31 wherein said virus producing cells are SV40 or polyoma virus.