Compositions and methods for regulating angiogenesis
In accordance with the present invention, EC progenitors can be used in a method for regulating angiogenesis, i.e., enhancing or inhibiting blood vessel formation, in a selected patient and in some preferred embodiments for targeting specific locations. For example, the EC progenitors can be used to enhance angiogenesis or to deliver an angiogenesis modulator, e.g. anti- or pro-angiogenic agents, respectively to sites of pathologic or utilitarian angiogenesis. Additionally, in another embodiment, EC progenitors can be used to induce reendothelialization of an injured blood vessel, and thus reduce restenosis by indirectly inhibiting smooth muscle cell proliferation.
1. A method for reducing peripheral vascular trauma during a stent or angioplasty procedure, comprising performing a stent or angioplasty procedure on a patient and administering to the patient, before or after the procedure, a pharmaceutical composition comprising a pharmaceutical carrier and a CD34 + , Flk-1 + , and tie-2 + endothelial cell (EC) progenitor which comprises or is coupled to a cytotoxic agent, a label, a co-stimulatory molecule for stimulating an immune reaction, an angiogenesis inhibitor, a recombinant endothelial cell mitogen or an antitumor drug.
2. The method of claim 1 , wherein the recombinant endothelial cell mitogen is selected from the group consisting of acidic FGF, basic FGF (bFGF), vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), transforming growth factor αand β (TGF-α and TGF-β), platelet-derived endothelial growth factor (PD-ECGF), platelet-derived growth factor (PDGF), tumor necrosis factor α (TNF-α), hepatocyte growth factor (HGF), insulin like growth factor (IGF), erythropoietin, colony stimulating factor (CSF), macrophage-CSF (M-CSF), granulocyte/macrophage CSF (GM-CSF) and nitric oxide synthase (NOS).
3. The method of claim 1 , wherein the recombinant endothelial cell mitogen is VEGF or bFGF.
4. The method of claim 3 , wherein the recombinant endothelial cell mitogen is VEGF and bFGF.
5. The method of claim 1 , wherein the recombinant endothelial cell mitogen is VEGF.
6. The method of claim 1 , wherein the composition is administered to the patient before the procedure.
7. The method of claim 1 , wherein the composition is administered to the patient after the procedure.