Bone marrow origin progenitor cell or endothelial progenitor cell in combination with DNMT1 gene therapy for vascular repair in metabolic disease
View Patent ↗The present invention provides an isolated population of bone marrow-derived endothelial progenitor cells (EPCs) and uses thereof for the treatment of vascular diseases.
1. A method of treating a vascular disease in a subject, the method comprising:
administering to a subject in need thereof, wherein the subject has a metabolic disorder an effective amount of CD34 + /Vascular Endothelial Growth Factor Receptor-2 + (VEGFR2 + ) bone marrow-derived endothelial progenitor cells (EPCs) to the subject with a metabolic disorder in need thereof,
wherein the bone marrow-derived EPCs are genetically modified by gene transfer, and
wherein the gene is DNA Methyltransferase-1 (DNMT1).
2. The method of claim 1 , wherein the vascular disease is associated with endothelial injury.
3. The method of claim 1 , wherein the vascular disease is hyperhomocysteinemia (HHcy), hyperlipidemia and diabetes associated vascular injury.
4. The method of claim 1 , wherein the bone marrow-derived EPCs are enriched for CD34 + /VEGFR2 + .
5. The method of claim 1 , wherein the bone marrow-derived EPCs are modified prior to administration to the subject.
6. The method of claim 1 , wherein the bone marrow-derived EPCs are modified during or after administration to the subject.
7. The method of claim 1 , wherein the bone marrow-derived EPCs are administered to the subject by at least one of direct injection, venous infusion, and arterial infusion.
8. The method of claim 1 , wherein the bone marrow-derived EPCs differentiate into endothelial cells in the subject.
9. The method of claim 1 , wherein the subject is also treated, either serially or in parallel, with a combination therapy.
10. The method of claim 9 , wherein the combination therapy comprises administering to the subject at least one active agent selected from the group consisting of a therapeutic agent, an anti-angiogenic or anti-vascular agent, an anti-inflammation agent, a VEGF inhibitor, an antibiotic, an anti-viral agent, an anti-fungal agent, an anti-protozoal agents, a hormone, a radioactive agent, a toxin, an anesthetic, and any combinations thereof.