Mesenchymal stem cells for prevention and treatment of immune responses in transplantation

• US 6,368,636 B1
• Filed: 10/26/1999
• Issued: 04/09/2002
• Est. Priority Date: 03/18/1998
• Status: Expired due to Term

• Current Assignee: Mesoblast International Srl
• Original Assignee: Osiris Therapeutics Incorporated (Smith & Nephew PLC)
• Inventors: Klyushnenkova, Elena N., Mosca, Joseph D., McIntosh, Kevin R.
• Primary Examiner(s): Saunders, David
• Assistant Examiner(s): Tung, Mary Beth
• Application Number:
  US09/427,333
• Time in Patent Office: 896 Days
• Field of Search: 435/372, 424/93.7, 424/572, 424/577
• US Class Current: 424/577
• CPC Class Codes: A61K 2035/122 for inducing tolerance or supression of immune responses
• CPC Class Codes: A61K 2035/124 the cells being hematopoietic, bone marrow derived or blood cells
• CPC Class Codes: A61K 2039/515 Animal cells
• CPC Class Codes: A61K 2039/5158 Antigen-pulsed cells, e.g. T-cells
• CPC Class Codes: A61K 35/28 Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
• CPC Class Codes: A61K 39/001 Preparations to induce tolerance to non-self, e.g. prior to transplantation
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C12N 2501/24 Interferons [IFN]
• CPC Class Codes: C12N 2502/1358 Bone marrow mesenchymal stem cells (BM-MSC)
• CPC Class Codes: C12N 5/0636 T lymphocytes
• CPC Class Codes: C12N 5/0663 Bone marrow mesenchymal stem cells (BM-MSC)

Abstract

A method of reducing an immune response to a transplant in a recipient by treating said recipient with an amount of mesenchymal stem cells effective to reduce or inhibit host rejection of the transplant. The mesenchymal stem cells can be administered before, at the same time as, or after the transplant. Also disclosed is a method of inducing a reduced immune response against a host by foreign tissue, i.e., graft versus host disease, by treatment with mesenchymal stem cells.

Claims

1. A process for reducing an immune response of effector cells against an alloantigen, comprising contacting effector cells with a supernatant of mesenchymal stem cells in an amount effective to reduce an immune response against an alloantigen whereby said effector cells upon contact with an alloantigen have a reduced immune response against said alloantigen.

2. The process of claim 1 wherein said effector cells are T cells.

3. The process of claim 2 wherein the T cells are from the donor and the alloantigen is from the recipient.

4. The process of claim 2 wherein the T cells are from the recipient and The alloantigen is from the donor.

5. The process of claim 2 wherein said T cells are present in a transplant.

6. The process of claim 2 wherein said supernatant is administered to a transplant recipient suffering from graft-versus-host disease.

7. The process of claim 2 wherein prior to said administration said mesenchymal stem cells (MSCs) have been expanded in culture.

8. The process of claim 2 wherein said effector cells are T cells previously activated and said immune response is the reactivation of said T cells.

9. The process of claim 5 wherein the transplant is skin.

10. The process of claim 5 wherein the supernatant of mesenchymal stem cells is administered to the transplant recipient to treat rejection of the transplant by the recipient.

11. The process of claim 2 wherein the mesenchymal stem cells are human mesenchymal stem cells.

12. The process of claim 2 further comprising administering to the recipient immunosuppressive agents.

13. The process of claim 5 wherein the transplant is a solid organ.

14. The process of claim 13 wherein the solid organ is selected from heart, pancreas, kidney, lung or liver.

15. The process of claim 5 wherein said supernatant is administered prior to said transplant.

16. The process of claim 5 wherein said supernatant is administered concurrently with said transplant.

17. The process of claim 5 wherein said supernatant is administered as part of said transplant.

18. The process of claim 5 wherein the supernatant is administered subsequent to said transplant.

19. The process of claim 2 wherein said supernatant is administered intravenously to the recipient.

20. The process of claim 2 wherein said effector cells are cells of a recipient of said donor transplant.

21. The process of claim 1 wherein the supernatant is obtained from mesenchymal stem cells co-cultured with T cells undergoing a mixed lymphocyte reaction.

22. A process for treating a transplant recipient to reduce in said recipient an immune response of effector cells against an alloantigen to the effector cells, comprising:

transplanting to a transplant recipient a transplant treated with a supernatant of mesenchymal stem cells in an amount effective to reduce an immune response of effector cells against an alloantigen to the effector cells, whereby in the transplant recipient the effector cells have a reduced immune response against the alloantigen.

23. The process of claim 22 wherein said effector cells are T cells.

24. A process for treating a transplant recipient to reduce in said recipient an immune response of effector cells against an alloantigen to the effector cells, comprising:

administering to a transplant recipient a supernatant of a mesenchymal stem cells in an amount effective to reduce an immune response of effector cells against an alloantigen to the effector cells, whereby in the transplant recipient the effector cells have a reduced immune response against the alloantigen.

25. A process of treating a transplant recipient for graft versus host disease, comprising treating the recipient of a donor transplant with a supernatant from a mesenchymal stem cell culture in an amount effective to reduce an immune response against the recipient by the transplant.