Modulating angiogenesis

• US 20030180265A1
• Filed: 03/18/2003
• Published: 09/25/2003
• Est. Priority Date: 03/21/2002
• Status: Active Grant

• Current Assignee: University of Florida Research Foundation, Incorporated (State University System of Florida)
• Original Assignee: University of Florida Research Foundation, Incorporated (State University System of Florida)
• Inventors: Grant, Maria, Scott, Edward W., May, W. Stratford
• Granted Patent: US 7,491,389 B2
• Time in Patent Office: Days
• US Class Current: 424/93.7
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 35/12 Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells vaccines or medicinal preparations containing antigens or antibodies A61K39/00
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07K 16/24 against cytokines, lymphokines or interferons
• CPC Class Codes: C12N 5/0692 Stem cells; Progenitor cells; Precursor cells

Abstract

Hemangioblasts in adult bone marrow participate in new blood vessel formation. By modulating the differentiation of hemangioblasts into blood vessel cells, angiogenesis in a particular tissue can be increased or decreased. Intravitreal injection of antibodies that block SDF-1 activity inhibited induced retinal neovascularization mediated by hemangioblasts.

Claims

1. A method for modulating angiogenesis in a target tissue in a subject, the method comprising a non-naturally occurring step of modulating the level of differentiation of hemangioblasts to blood vessel cells in the subject.

2. The method of claim 1, wherein the step of modulating the level of differentiation of hemangioblasts to blood vessel cells in the subject comprises increasing or decreasing the number of hemangioblasts in the subject.

3. The method of claim 2, wherein the step of modulating the level of differentiation of hemangioblasts to blood vessel cells in the subject comprises increasing the number of hemangioblasts in the subject.

4. The method of claim 3, wherein the step of increasing the number of hemangioblasts in the subject is performed by administering hemangioblasts to the subject.

5. The method of claim 4, wherein hemangioblasts administered to the subject are derived from cells that were removed from the subject.

6. The method of claim 5, wherein the cells that were removed from the subject were expanded in vitro prior to being administered to the subject.

7. The method of claim 4, wherein hemangioblasts administered to the subject are derived from cells from a donor other than the subject.

8. The method of claim 7, wherein the cells from the donor were expanded in vitro prior to being administered to the subject.

9. The method of claim 2, wherein the step of modulating the level of differentiation of hemangioblasts to blood vessel cells in the subject comprises decreasing the number of hemangioblasts in the subject.

10. The method of claim 9, wherein the step of decreasing the number of hemangioblasts in the subject comprises administering to the subject an agent that depletes hemangioblasts.

11. The method of claim 10, wherein the agent is an antibody that specifically binds a molecule present on the surface of hemangioblasts.

12. The method of claim 1, wherein the step of modulating the level of differentiation of hemangioblasts to blood vessel cells in the subject comprises increasing or decreasing the recruitment of hemangioblasts from bone marrow to a non-bone marrow compartment.

13. The method of claim 12, wherein the step of modulating the level of differentiation of hemangioblasts to blood vessel cells in the subject comprises increasing the recruitment of hemangioblasts from bone marrow to a non-bone marrow compartment.

14. The method of claim 12, wherein the step of modulating the level of differentiation of hemangioblasts to blood vessel cells in the subject comprises decreasing the recruitment of hemangioblasts from bone marrow to a non-bone marrow compartment.

15. A method for decreasing blood vessel formation in a subject, the method comprising the step of administering to the subject an agent that blocks the activity of SDF-1.

16. The method of claim 15, wherein the agent is an antibody that specifically binds SDF-1.

17. The method of claim 15, wherein the agent is administered to an eye of the subject.

18. The method of claim 16, wherein the agent is administered to an eye of the subject.

19. A hemangioblast isolated from adult bone marrow.

20. The hemangioblast of claim 19, wherein the adult bone marrow is mammalian bone marrow.

21. A method for isolating an hemangioblast from the bone marrow of an adult animal, the method comprising the steps of:

(a) isolating bone marrow from the animal, wherein the bone marrow comprises at least one hemangioblast and at least one non-hemangioblast cell;

(b) separating the at least one hemangioblast and the at least one non-hemangioblast cell; and

(c) collecting the at least one hemangioblast.

22. The method of claim 21, wherein the step (b) of separating the at least one hemangioblast and the at least one non-hemangioblast cell comprises contacting the bone marrow with an agent that specifically binds the at least one hemangioblast but not the at least one non-hemangioblast cell.

23. The method of claim 21, wherein the step (b) of separating the at least one hemangioblast and the at least one non-hemangioblast cell comprises contacting the bone marrow with an agent that specifically binds the at least one non-hemangioblast cell but not the at least one hemangioblast.

24. The method of claim 22, wherein the agent is an antibody.

25. The method of claim 23, wherein the agent is an antibody.