Connective tissue regeneration using human mesenchymal stem cell preparations

• US 5,811,094 A
• Filed: 04/11/1995
• Issued: 09/22/1998
• Est. Priority Date: 11/16/1990
• Status: Expired due to Term

• Current Assignee: Mesoblast International Srl
• Original Assignee: Osiris Therapeutics Incorporated (Smith & Nephew PLC)
• Inventors: Caplan, Arnold I., Haynesworth, Stephen E.
• Primary Examiner(s): Lankford, Jr., Leon B.
• Application Number:
  US08/420,297
• Time in Patent Office: 1,260 Days
• Field of Search: 424/93.7, 435/372, 435/366
• US Class Current: 424/93.7
• CPC Class Codes: A61F 2/28 Bones joints A61F2/30
• CPC Class Codes: A61F 2/30756 Cartilage endoprostheses A61F2/3603 takes precedence
• CPC Class Codes: A61K 2035/124 the cells being hematopoietic, bone marrow derived or blood cells
• 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 35/28 Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
• CPC Class Codes: A61L 2430/10 for reconstruction of tendons or ligaments
• CPC Class Codes: A61L 27/3834 Cells able to produce different cell types, e.g. hematopoietic stem cells, mesenchymal stem cells, marrow stromal cells, embryonic stem cells
• CPC Class Codes: A61L 27/3843 Connective tissue
• CPC Class Codes: A61L 27/3895 using specific culture conditions, e.g. stimulating differentiation of stem cells, pulsatile flow conditions
• CPC Class Codes: A61L 31/005 Ingredients of undetermined constitution or reaction products thereof
• CPC Class Codes: C07K 16/28 against receptors, cell surface antigens or cell surface determinants
• CPC Class Codes: C12N 2501/23 Interleukins [IL]
• CPC Class Codes: C12N 2501/2301 Interleukin-1 (IL-1)
• CPC Class Codes: C12N 2501/39 Steroid hormones
• CPC Class Codes: C12N 2533/18 Calcium salts, e.g. apatite, Mineral components from bones, teeth, shells
• CPC Class Codes: C12N 5/0068 General culture methods using substrates for specific animal cell type C12N5/06
• CPC Class Codes: C12N 5/0663 Bone marrow mesenchymal stem cells (BM-MSC)

Abstract

Isolated human mesenchymal stem cells, a method for isolating, purifying, and culturally expanding human mesenchymal stem cells (i.e. mesenchymal stem cells or "MSCs"), and characterization of (including by cytokine expression profiling) and uses, particularly research reagent, diagnostic and therapeutic uses for such cells. The stem cells can be culture expanded without differentiating. Monoclonal antibodies specific for human mesenchymal stem cells and the monoclonal hybridoma cell lines (ATCC nos. 10743-10745) that synthesize and secrete these monospecific antibodies, and uses of the monoclonal antibodies for diagnostic and/or therapeutic purposes.

Claims

1. A method of producing a connective tissue which comprises producing connective tissue in an individual in need thereof by administering to said individual a cell preparation containing human mesenchymal stem cells which is recovered from human bone marrow and which is substantially free of blood cells.

2. The method of claim 1 wherein the step of administering the cell preparation comprises applying said cell preparation to an area of a connective tissue defect.

3. The method of claim 1 wherein the mesenchymal stem cells are recovered from the individual being treated.

4. The method of claim 2 which further comprises administering a factor which stimulates differentiation of the mesenchymal stem cells into the type of connective tissue necessary for repair of said defect.

5. The method of claim 1 wherein the mesenchymal stem cells have been culture-expanded.

6. The method of claim 2 wherein the defect is a bone defect.

7. The method of claim 2 wherein the defect is a cartilage defect.

8. The method of claim 1 wherein the cell preparation is administered with a factor which induces differentiation of the human mesenchymal stem cells into said connective tissue.

9. The method of claim 1 wherein the tissue is skeletal tissue.

10. The method of claim 1 wherein the mesenchymal stem cells are essentially homogeneous.

11. The method of claim 2 wherein the cell preparation is administered in conjunction with a carrier.

12. The method of claim 1 wherein the connective tissue is stroma.

23. The method of claim 1 wherein the connective tissue is selected from the group consisting of bone, cartilage, ligament, tendon and muscle.

13. A method for producing a connective tissue comprising producing connective tissue in an individual in need thereof by administering to said individual an isolated cell preparation which has been enriched in human mesenchymal stem cells.

14. The method of claim 13 wherein the step of administering the cell preparation comprises applying said cell preparation to an area of a connective tissue defect.

15. The method of claim 13 wherein the mesenchymal stem cells are recovered from the individual being treated.

16. The method of claim 14 which further comprises administering a factor which stimulates differentiation of the mesenchymal stem cells into the type of connective tissue necessary for repair of said defect.

17. The method of claim 13 wherein the mesenchymal stem cells have been culture-expanded.

18. The method of claim 14 wherein the defect is a bone defect.

19. The method of claim 14 wherein the defect is a cartilage defect.

20. The method of claim 13 wherein the cell preparation is administered with a factor which induces differentiation of the human mesenchymal stem cells into said connective tissue.

21. The method of claim 13 wherein the mesenchymal stem cells are essentially homogeneous.

22. The method of claim 13 wherein the connective tissue is stroma.

24. A method for enhancing the implantation of a prosthetic device in connective tissue comprising the step of implanting a prosthetic device having human mesenchymal stem cells adhered thereto under conditions suitable for differentiating the cells into connective tissue.

25. The method of claim 24 wherein the conditions are suitable for differentiating the cells into skeletal tissue.

26. The method of claim 25 wherein the mesenchymal stem cells are in a cell preparation which is recovered from human bone marrow and which is substantially free of blood cells.

27. The method of claim 26 wherein the mesenchymal progenitor cells have been culture-expanded.