Human mesenchymal stem cells

• US 6,387,367 B1
• Filed: 05/28/1999
• Issued: 05/14/2002
• Est. Priority Date: 05/29/1998
• Status: Expired due to Term

• Current Assignee: Mesoblast International Srl
• Original Assignee: Osiris Therapeutics Incorporated (Smith & Nephew PLC)
• Inventors: Craig, Stewart, Davis-Sproul, Janice M., McNeil, Renee Marie, Hammill, Lora Catherine, Moorman, Mark Aaron, Simonetti, Donald William Jr.
• Primary Examiner(s): Priebe, Scott D.
• Assistant Examiner(s): Sorbello, Eleanor
• Application Number:
  US09/321,924
• Time in Patent Office: 1,082 Days
• Field of Search: 424/93.21, 424/93.1, 424/93.2, 435/320.1, 435/325, 435/7.1, 514/44, 530/387.1, 536/23.1, 536/23.5
• US Class Current: 424/93.1
• CPC Class Codes: A61K 2035/124 the cells being hematopoietic, bone marrow derived or blood cells
• 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 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 5/0663 Bone marrow mesenchymal stem cells (BM-MSC)

Abstract

Human mesenchymal stem cells having the phenotype SH3+, CD45+ can be isolated. These precursor mesenchymal item cells are useful for treatment of patients in need of mensenchymal stem cell.

Claims

1. An isolated population of human mesenchymal stem cells comprising human mesenchymal stem cells which have been enriched for CD45+ human mesenchymal stem cells.

2. The isolated population of human mesenchymal stem cells of claim 1 wherein the human mesenchymal stem cells which are CD45+ are further reactive with at least one monoclonal antibody selected from the group consisting of SH2 antibody, SH3 antibody and SH4 antibody.

3. The isolated cell population of claim 2 wherein the human mesenchymal stem cells are SH3+ and CD45+.

4. The isolated cell population of claim 2 wherein the human mesenchymal stem cells are SH2+ and CD45+.

5. A composition comprising an isolated population of human mesenchymal stem cells which bear a fibroblast surface marker and have been enriched for CD45+ human mesenchymal stem cell.

6. The composition of claim 5 further comprising CD14+ cells.

7. A process of isolating a population of human mesenchymal stem cells which are CD45+, comprising

(a) obtaining an enriched population of human mesenchymal stem cells;

and

(b) selecting from the cell population of (a) cells that are CD45+.

8. A process of isolating a population of human mesenchymal stem cells which are SH3+ and CD45+, comprising

(a) obtaining an enriched population of human mesenchymal stem cells that are SH3+;

and

(b) selecting from the cell population of (a) cells that are CD45+.

9. A process of isolating a population of human mesenchymal stem cells which are SH2+ and CD45+, comprising

(a) obtaining an enriched population of human mesenchymal stem cells that are SH2+;

and

(b) selecting from the cell population of (a) cells that are CD45+.

10. A process of isolating a population of human mesenchymal stem cells which bear fibroblast surface markers comprising

(a) obtaining an enriched population of human mesenchymal stem cells;

and

(b) selecting from the cell population of (a) cells that are fibroblast+.

11. The method of claim 10, further comprising selecting from the cell population bearing fibroblast surface markers cells that are SH3+.

12. The method of claim 11, further comprising selecting from the cell population bear fibroblast surface markers and are SH3+, cells that are CD45+.

13. A method for treating a patient in need of mesenchymal stem cells, comprising administering human mesenchymal stem cells which are CD45+ to said patient.

14. The method of claim 13 wherein the human mesenchymal stem cells are SH3+ and CD45+.

15. The method of claim 13 wherein the human mesenchymal stem cells are SH2+ and CD45+.

16. The method of claim 13 wherein the mesenchymal stem cells are administered to generate bone formation.

17. The method of claim 13 wherein the mesenchymal stem cells are administered to treat or repair a connective tissue defect in the patient.

18. The method of claim 17 wherein the defect is a bone defect.

19. The method of claim 17 wherein the defect is a cartilage defect.

20. The method of claim 13 wherein the mesenchymal stem cells are administered to enhance hematopoietic stem or progenitor cell engraftment in an individual in need thereof.

21. A method of treating a patient in need of mesenchymal stem cells, comprising administering human mesenchymal stem cells which bear fibroblast surface markers to said patient.

22. Isolated CD45+ human mesenchymal stem cells transfected with exogenous genetic material encoding a protein to be expressed.