Isolation and mobilization of stem cells expressing vegfr-1

• US 20050026220A1
• Filed: 08/12/2002
• Published: 02/03/2005
• Est. Priority Date: 08/10/2001
• Status: Abandoned Application

• Current Assignee: Cornell Research Foundation Incorporated (Cornell University), Imclone Systems Incorporated
• Original Assignee: Cornell Research Foundation Incorporated (Cornell University)
• Inventors: Rafii, Shahin, Witte, Larry
• Application Number:
  US10/484,511
• Publication Number:
  US 20050026220A1
• Time in Patent Office: Days
• US Class Current: 435/7.200
• 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: A61P 1/18 for pancreatic disorders, e.g. pancreatic enzymes
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/06 Antianaemics
• 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 14/52 Cytokines; Lymphokines; Interferons
• CPC Class Codes: C12N 2501/165 Vascular endothelial growth factor [VEGF]
• CPC Class Codes: C12N 5/0647 Haematopoietic stem cells; Uncommitted or multipotent progenitors

Abstract

The present invention is directed to methods of isolating mammalian stem cells expressing the VEGF receptor VEGFR-1 and compositions thereof. The present invention is also directed to methods of using such isolated mammalian stem cells expressing VEGFR-1 to treat various conditions, which can involve inducing hematopoiesis, vasculogenesis and/or angiogenesis, myogenesis, and neurogenesis to treat the various condition. Finally, the present invention is directed to therapeutic methods using a molecule that binds and activates or stimulates VEGFR-1, for example, P1GF, to stimulate proliferation and/or differentiation and mobilization, i.e., motogenesis, of stem cells.

Claims

1. A method for isolation of mammalian stem cells comprising

providing a population of cells;

contacting the population of cells with a molecule that specifically binds VEGFR-1; and

isolating cells that bind the molecule that specifically binds VEGFR-1.

2. The method of claim 1, wherein the population of cells is isolated from a fetal liver, umbilical cord blood, a yolk sac, a mature spinal cord, bone marrow, or an adult peripheral blood sample.

3. The method of claim 1, wherein the population of cells is isolated from central nervous system.

4. The method of claim 1, wherein the molecule that specifically binds VEGFR-1 is an antibody.

5. The method of claim 1, wherein the molecule that specifically binds VEGFR-1 is a ligand.

6. The method of claim 5, wherein the ligand is PlGF.

7. The method of claim 1, wherein the method further comprises

contacting the cells with one or more positive selection markers and

isolating cells that bind the one or more positive selection markers.

8. The method of claim 7, wherein the positive selection marker is CD34 or AC133.

9. The method of claim 1, wherein the method further comprises

contacting the cells with one or more negative selection markers and

isolating cells that do not bind the one or more negative selection markers.

10. The method of claim 9, wherein the negative selection marker is CD38 or Lin.

11. The method of claim 1, wherein the cells isolated are human stem cells.

12. The method of claim 11, wherein the human stem cells are hematopoietic stem cells.

13. The method of claim 11, wherein the human stem cells are endothelial, muscle, or neural stem cells.

18. A composition comprising a cell expressing VEGFR-1, wherein the cell expressing VEGFR-1 is isolating using the method of claim 1.

19. A method of treating a mammal comprising administering to the mammal a composition of claim 1.

20. The method of claim 19, wherein the treatment involves induction of hematopoiesis, vasculogenesis and/or angiogenesis, or myogenesis and/or neurogenesis.

21. The method of claim 19, wherein the treatment involves mobilization of stem cells to the area of administration.

22. The method of claim 19, wherein the treatment involves stimulation of stem cells to proliferate or differentiate.

23. The method of claim 19, wherein the treatment is useful to reconstitute pancreatic islet cells or regenerate damaged neurons.

24. The method of claim 19, wherein the method is useful to treat cardiac or peripheral ischemia.

14. A composition comprising a molecule that specifically binds VEGFR-1.

15. The composition of claim 14, wherein the molecule that specifically binds VEGFR-1 is an antibody.

16. The composition of claim 15, wherein the molecule that specifically binds VEGFR-1 is a ligand.

17. The composition of claim 16, wherein the ligand is PlGF.