Compositions and methods for regulating angiogenesis
AssigneeSteward St. Elizabeth's Medical Center of Boston, Inc.
InventorsJeffrey M. Isner, Takayuki Asahara, Douglas W. Losordo
Life of this patent
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Abstract
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.
Claims19
A method for delivering an endothelial progenitor cell to a site of angiogenesis in a human patient, the method comprising:
- administering to the patient a composition comprising a human CD34+ cell, wherein the composition is enriched for human CD34+ cells relative to peripheral blood, and wherein the endothelial progenitor cell is isolated using an antibody specific for human CD34, and a polypeptide selected from the group consisting of acidic FGF, basic FGF, vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), transforming growth factor α and 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).
A method for improving or preserving left ventricular (LV) function in a human patient comprising injecting into the left ventricle of a heart a composition comprising human CD34+ cells, wherein the composition is enriched for human CD34+ cells relative to peripheral blood and wherein the endothelial progenitor cells are isolated using an antibody specific for human CD34.
A method for improving or preserving cardiac function in a human patient comprising identifying an area of hibernating cardiac tissue in a heart and contacting the tissue with a composition comprising endothelial progenitor cells that are isolated using an antibody specific for human CD34, wherein the composition is enriched for human CD34+ cells relative to peripheral blood.
A method for incorporating endothelial progenitor cells into a cardiac tissue in a patient comprising administering endothelial progenitor cells which are isolated as CD34+ to a heart.
A method of treating myocardial ischemia or ischemic cardiomyopathy in a patient in need thereof, the method comprising administering to cardiac tissue an effective amount of endothelial progenitor cells isolated as CD34+ via site-directed delivery.
A method for delivering an endothelial progenitor cell to an ischemic cardiac tissue in a patient, the method comprising isolating a CD34+ endothelial progenitor cell and using site-directed delivery to deliver said cell to the tissue.
A method for delivering an endothelial progenitor cell to a site of angiogenesis in a human patient, the method comprising:
- administering to the patient a composition comprising a human CD34+ cell, wherein the composition is enriched for human CD34+ cells relative to peripheral blood, wherein the endothelial progenitor cell is isolated using an antibody specific for human CD34, and wherein the composition comprises at least about 15% CD34+ cells, and a polypeptide selected from the group consisting of acidic FGF, basic FGF, vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), transforming growth factor α and 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).
A method for delivering an endothelial progenitor cell to a site of angiogenesis in a human patient, the method comprising:
- administering to the patient a composition comprising 106-108 endothelial progenitor cells, wherein the endothelial progenitor cells are isolated as CD34+, and wherein the endothelial progenitor cell is isolated using an antibody specific for human CD34, and a polypeptide selected from the group consisting of acidic FGF, basic FGF, vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), transforming growth factor α and 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).
Dependencies are inferred from the claim text.