Heparan sulphate

Patent metadata

Field	Value
Publication number	US-9044496-B2
Application number	US-201113267216-A
Country	US
Kind code	B2
Filing date	Oct 6, 2011
Priority date	Oct 8, 2010
Publication date	Jun 2, 2015
Grant date	Jun 2, 2015

Abstract

Heparan sulphate from bone marrow stroma is disclosed together with the use of heparan sulphate from bone marrow stroma in the differentiation and/or lineage commitment of stem cells.

First claim

The invention claimed is:

1. Heparan sulphate HS5 substantially purified from the core protein, wherein the heparan sulphate has the following heparan lyase disaccharide digestion profile:

Disaccharide
% Composition

ΔHexUA - GlcN
22.11 ± 10%

ΔHexUA - GlcN,6S
38.79 ± 10%

ΔHexUA - GlcNS
 4.20 ± 10%

ΔHexUA - GlcNAc,6s
 4.53 ± 10%

Other
 30.37 ± 10%.

2. A method of increasing the number of committed clonogenic cells in a population of hematopoietic stem cells (HSCs), the method comprising culturing HSCs in vitro in the presence of heparan sulphate according to claim 1 .

3. The method of claim 2 wherein the method comprises increasing the number of myeloid lineage-committed progenitor cells.

4. The method of claim 2 wherein the method comprises increasing the number of colony forming cells (CFC).

5. The method of claim 2 wherein the method comprises increasing the number of burst forming unit-erythroid (BFU-E).

6. The method of claim 2 wherein the method comprises increasing the number of colony forming unit-granulocyte macrophage (CFU-GM).

7. The method of claim 2 wherein the initial HSC population in the culture comprises at least 50% CD34+ cells.

8. The method of claim 2 wherein the HSC population is obtained from cord blood.

9. A method of promoting osteogenesis, the method comprising administering heparan sulphate according to claim 1 to osteoprogenitor cells.

10. Culture media comprising heparan sulphate according to claim 1 .

11. A method of transplanting hematopoietic stem cells (HSCs) to a patient in need thereof, the method comprising transplanting a therapeutically effective amount of HSCs to the patient and administering a therapeutically effective amount of heparan sulphate according to claim 1 to the site of transplantation of the HSCs in the patient or to tissue that surrounds, is near to, or adjacent to the site of transplantation.

12. The method of claim 11 wherein the HSCs and heparan sulphate are administered in combination.

13. The method of claim 11 wherein the HSCs and heparan sulphate are administered separately.

14. A biocompatible implant or prosthesis comprising a biomaterial and heparan sulphate according to claim 1 .

15. A method of treating a bone fracture in a patient, the method comprising administration of a therapeutically effective amount of heparan sulphate according to claim 1 to the patient.

16. The method of claim 15 wherein the method comprises administering said heparan sulphate to the tissue surrounding the fracture.

17. The method of claim 15 wherein administration of said heparan sulphate comprises injection of the heparan sulphate to the tissue surrounding the fracture.

18. The method of claim 15 wherein said heparan sulphate is formulated as a pharmaceutical composition or medicament comprising the heparan sulphate and a pharmaceutically acceptable carrier, adjuvant or diluent.

19. A method of treating a bone fracture in a patient, the method comprising surgically implanting a biocompatible implant or prosthesis, which implant or prosthesis comprises a biomaterial and a therapeutically effective amount of heparan sulphate according to claim 1 , into tissue of the patient at or surrounding the site of fracture.

20. Heparan sulphate according to claim 1 wherein the heparan sulphate is isolated from human bone marrow stroma.

Assignees

• Cool Simon
• Nurcombe Victor
• Agency Science Tech & Res

Inventors

• Cool Simon
• Nurcombe Victor

Classifications

• C12N5/0647

  Haematopoietic stem cells; Uncommitted or multipotent progenitors · CPC title

• A61K31/727 Primary

  Heparin; Heparan · CPC title

• C08B37/0075

  Heparin; Heparan sulfate; Derivatives thereof, e.g. heparosan; Purification or extraction methods thereof · CPC title

• C12N2500/34

  Sugars · CPC title

• A61P19/00

  Drugs for skeletal disorders · CPC title