Methods for mobilizing mesenchymal stem cells in a patient
The current invention provides a method for mobilizing endothelial progenitor cells (EPC) and/or mesenchymal stem cells (MSC) in a patient, wherein the method comprises the steps of (i) administering a vascular endothelial growth factor receptor (VEGFR) agonist to the patient; and (ii) administering an antagonist of CXCR4 to the patient. Also provided are uses of EPC and MSC harvested using the methods of the invention.
1. A method for mobilizing mesenchymal stem cells (MSC) in a patient, wherein the method comprises the steps of (i) administering a VEGFR agonist to the patient; and (ii) administering an antagonist of CXCR4 to the patient.
2. The method of claim 1 wherein the VEGFR agonist is a VEGFR-2 agonist.
3. A method for mobilizing mesenchymal stem cells (MSC) in a patient with elevated circulating levels of VEGF, wherein the method comprises administering an antagonist of CXCR4 to the patient.
4. The method of claim 3 wherein the method further comprises administering a VEGFR-1 antagonist.
5. The method of claim 4 wherein the VEGFR-1 antagonist is an antibody or fragment thereof.
6. The method of claim 1 , wherein the antagonist of CXCR4 is AMD3100.
7. The method of claim 1 , wherein the method further includes harvesting MSC.
8. The method of claim 7 , wherein the harvested MSC are cultivated in vitro.
9. The method of claim 8 , wherein the cultivated cells are administered back to the patient or to another patient.
10. The method of claim 8 , wherein the cultivated cells are genetically modified.
11. The method of claim 10 , wherein the genetically modified cells are more resistant to apoptosis than the wild-type cells.
12. The method of claim 9 , wherein the cultivated cells are targeted to damaged tissue in the recipient of said cultivated cells.
13. The method of claim 12 , wherein the damaged tissue is damaged by ischemia, radiotherapy, chemotherapy, auto-immune disease or physical injury.
14. The method of claim 1 or claim 3 further comprising mobilizing endothelial progenitor cells (EPC).
15. A method for mobilizing mesenchymal stem cells (MSC) from the bone marrow of a patient, wherein the method comprises the steps of (i) administering a VEGFR agonist to the patient; and (ii) administering an antagonist of CXCR4 to the patient.
16. A method for mobilizing mesenchymal stem cells (MSC) in a patient, wherein the method comprises the steps of (i) chronically administering a VEGFR agonist to the patient; and (ii) administering an antagonist of CXCR4 to the patient.
17. A method for mobilizing mesenchymal stem cells (MSC) in a patient, wherein the method comprises the steps of (i) administering a VEGFR agonist to the patient; and (ii) acutely administering an antagonist of CXCR4 to the patient.
18. The method of claim 17 wherein the antagonist of CXCR4 is administered directly/locally to a perfused bone.
19. A method for mobilizing mesenchymal stem cells (MSC) in a patient, wherein the method comprises the steps of (i) administering a VEGF-E to the patient; and (ii) administering an antagonist of CXCR4 to the patient.