Osteoarthritis cartilage regeneration

• US 6,835,377 B2
• Filed: 05/13/1998
• Issued: 12/28/2004
• Est. Priority Date: 05/13/1998
• Status: Expired due to Term

• Current Assignee: Case Western Reserve University, Osiris Therapeutics Incorporated (Smith & Nephew PLC)
• Original Assignee: Osiris Therapeutics Incorporated (Smith & Nephew PLC)
• Inventors: Fink, David J., Burns, James S., Caplan, Arnold I., Barry, Francis P., Marshak, Daniel R., Goldberg, Victor M.
• Primary Examiner(s): Witz, Jean C.
• Application Number:
  US09/078,531
• Publication Number:
  US 20020110544A1
• Time in Patent Office: 2,421 Days
• Field of Search: 424/93.7, 435/366, 435/372
• US Class Current: 424/93.7
• CPC Class Codes: A61K 2035/124 the cells being hematopoietic, bone marrow derived or blood cells
• CPC Class Codes: A61K 2035/126 Immunoprotecting barriers, e.g. jackets, diffusion chambers
• CPC Class Codes: C12N 2501/15 Transforming growth factor beta (TGF-β)
• CPC Class Codes: C12N 2501/23 Interleukins [IL]
• CPC Class Codes: C12N 2501/39 Steroid hormones
• CPC Class Codes: C12N 2533/54 Collagen; Gelatin
• CPC Class Codes: C12N 5/0655 Chondrocytes; Cartilage
• CPC Class Codes: C12N 5/0663 Bone marrow mesenchymal stem cells (BM-MSC)

Abstract

For repair of cartilage damaged as part of the degenerative effects of osteoarthritis, the inventors have found that the human mesenchymal stem cell approach makes it possible to: (1) regenerate both shallow cartilage chondral defects and full thickness cartilage defects (osteochondral lesions); (2) broaden the suitable clinical population to routinely include middle-aged patients; (3) eliminate the use of autologous tissue grafts (mature cartilage and the periosteal covering) to repair an articular cartilage injury; (4) regenerate other types of injured cartilage such as patellar and spinal disk cartilage; (5) regenerate articular joint cartilage in older patients with osteoarthritis; and (6) form new cartilage and subchondral bone which fully integrate into the adjacent normal tissue.

Claims

1. A method for regenerating articular cartilage defects in a host in need thereof, comprising administering to said host cultured human mesenchymal stem cells, said human mesenchymal stem cells having a fibroblastic morphology.

2. The method of claim 1, wherein the method further comprises administering a biomatrix material.

3. The method of claim 1, wherein the method further comprises administering a contracting agent.

4. The method of claim 1, wherein the method further comprises administering a chondrogenesis promoting factor.

5. The method of claim 4, wherein the factor is TGF-β

3.

6. The method of claim 1, wherein the method further comprises administering IL-1 inhibitors.

7. The method of claim 1, further comprising administering osteochordral precursor cells.

8. The method of claim 1, wherein the cartilage defect comprises an articular cartilage injury.

9. The method of claim 1, wherein the biomatrix is selected from the group consisting of a collagen gel, a chemically cross-linked collagen gel, a fibrin gel, a fibrin glue, and an autologous fibrin gel.

10. The method of claim 8, wherein said administering is through arthroscopic injection.

11. The method of claim 1, wherein said cartilage defect comprises a lesion on an articular surface.

12. The method of claim 11, wherein the human mesenchymal stem cells are in a liquid suspension.

13. The method of claim 12, wherein said administering is by injection directly into a synovial cavity in proximity to a lesion.

14. The method of claim 12, wherein said liquid suspension further comprises serum or buffered saline.

15. The method of claim 2, wherein the cartilage defect comprises loss of cartilage at a joint.

16. The method of claim 15, wherein the biomatrix is a molded gel.

17. The method of claim 16, wherein said administering is by direct application to the joint surface.

18. A process for treating a cartilage defect resulting from osteoarthritis, comprising administering to a host in need thereof human mesenchymal stem cells in an amount effective to repair the cartilage defect, said human mesenchymal stem cells having a fibroblastic morphology.

19. The process of claim 18, wherein the amount of human mesenchymal stem cells is in the range of from about 0.1×

10⁸ to about 1×

10⁸ cells.