Intramyocardial injection of autologous bone marrow

Abstract

A method of treating cardiac or myocardial conditions comprises the administration of an effective amount of autologous bone marrow. The bone marrow may optionally be stimulated and/or administered in combination with a pharmaceutical drug, protein, gene or other factor or therapy that may enhance bone marrow production of angiogenic growth factors and/or promote endothelial cell proliferation or migration or blood vessel formation.

We claim:  
     
         1 . A method of enhancing collateral blood vessel formation which comprises the step of directly administering to a desired site an effective amount of autologous bone marrow.  
     
     
         2 . The method of  claim 1 , wherein the autologous bone marrow is injected.  
     
     
         3 . The method of  claim 1 , wherein the autologous bone marrow is injected intramyocardially.  
     
     
         4 . The method of  claim 3 , wherein the autologous bone marrow is injected trans-epicardially or trans-endocardially.  
     
     
         5 . The method of  claim 4 , wherein with the trans-endocardial approach a catheter-based approach is used.  
     
     
         6 . The method of  claim 1 , wherein the autologous bone marrow is injected peripherally into the limb intramuscularly.  
     
     
         7 . The method of  claim 1 , wherein the autologous bone marrow has been stimulated.  
     
     
         8 . The method of  claim 7 , wherein the autologous bone marrow has been stimulated by contact with one or more cytokines or other proteins or stimulating agents.  
     
     
         9 . The method of  claim 7 , wherein the cytokines are selected from the group consisting of HIF-1, EPAS1, MCP-1, and CM-CSF.  
     
     
         10 . The method of  claim 7 , wherein the autologous bone marrow has been transfected with vectors carrying relevant genes.  
     
     
         11 . The method of  claim 10 , wherein the autologous bone marrow has been transfected with a plasmid vector or an adenoviral vector, or any other vector demonstrated to be effective for gene transfer, carrying the HIF-1 or EPAS1 transgene, or any other transgene demonstrated to be effective in enhancing the capacity of bone marrow to induce angiogenesis.  
     
     
         12 . The method of  claim 7 , wherein the autologous bone marrow has been stimulated by transient exposure to hypoxia or a form of energy.  
     
     
         13 . The method of  claim 7 , wherein conditioned medium derived from autologous bone marrow growing in culture is injected into the ischemic heart or limb.  
     
     
         14 . The method of  claim 1 , wherein the autologous bone marrow is administered in combination with a pharmacological drug, protein, or gene or any other compound or therapy that may enhance bone marrow production of angiogenic growth factors and/or promote endothelial cell proliferation, migration, or blood vessel formation.  
     
     
         15 . The method of  claim 14 , wherein the autologous bone marrow and the other agent or agents are administered together.  
     
     
         16 . The method of  claim 14 , wherein the autologous bone marrow and the other agent or agents are combined prior to administration.  
     
     
         17 . The method of  claim 16 , wherein the autologous bone marrow has been stimulated.  
     
     
         18 . The method of  claim 1 , wherein ischemic tissue is treated.  
     
     
         19 . A method of promoting the development of newly implanted myocardial cells which comprises the step of directly administering an effective amount of autologous bone marrow.  
     
     
         20 . The method of  claim 19 , wherein the autologous bone marrow is injected.  
     
     
         21 . The method of  claim 19 , wherein the autologous bone marrow is injected intramyocardially.  
     
     
         22 . The method of  claim 21 , wherein the autologous bone marrow is injected trans-epicardially or trans-endocardially.  
     
     
         23 . The method of  claim 22 , wherein with the trans-endocardial approach a catheter-based approach is used.  
     
     
         24 . The method of  claim 19 , wherein the autologous bone marrow is injected peripherally into the limb intramuscularly.  
     
     
         25 . The method of  claim 19 , wherein the autologous bone marrow has been stimulated.  
     
     
         26 . The method of  claim 25 , wherein the autologous bone marrow has been stimulated by contact with one or more cytokines or other proteins or stimulating agents.  
     
     
         27 . The method of  claim 25 , wherein the cytokines are selected from the group consisting of HIF-1, EPAS1, MCP-1, and CM-CSF.  
     
     
         28 . The method of  claim 25 , wherein the autologous bone marrow has been transfected with vectors carrying relevant genes.  
     
     
         29 . The method of  claim 28 , wherein the autologous bone marrow has been transfected with a plasmid vector or an adenoviral vector, or any other vector demonstrated to be effective for gene transfer, carrying the HIF-1 or EPAS1 transgene, or any other transgene demonstrated to be effective in enhancing the capacity of bone marrow to induce angiogenesis.  
     
     
         30 . The method of  claim 25 , wherein the autologous bone marrow has been stimulated by transient exposure to hypoxia or a form of energy.  
     
     
         31 . The method of  claim 25 , wherein conditioned medium derived from autologous bone marrow growing in culture is injected into the ischemic heart or limb.  
     
     
         32 . The method of  claim 19 , wherein the autologous bone marrow is administered in combination with a pharmacological drug, protein, or gene or any other compound or therapy that may enhance bone marrow production of angiogenic growth factors and/or promote endothelial cell proliferation, migration, or blood vessel formation.  
     
     
         33 . The method of  claim 32 , wherein the autologous bone marrow and the other agent or agents are administered together.  
     
     
         34 . The method of  claim 32 , wherein the autologous bone marrow and the other agent or agents are combined prior to administration.  
     
     
         35 . The method of  claim 34 , wherein the autologous bone marrow has been stimulated.  
     
     
         36 . A method of improving the electrical conductivity of the heart of a patient with cardiac electrical pathway impairment, which comprises the step of administering an effective amount of autologous bone marrow.  
     
     
         37 . The method of  claim 36 , wherein the autologous bone marrow is injected.  
     
     
         38 . The method of  claim 36 , wherein the autologous bone marrow is injected intramyocardially.  
     
     
         39 . The method of  claim 38 , wherein the autologous bone marrow is injected trans-epicardially or trans-endocardially.  
     
     
         40 . The method of  claim 39 , wherein with the trans-endocardial approach a catheter-based approach is used.  
     
     
         41 . The method of  claim 36 , wherein with the trans-endocardial approach the autologous bone marrow is injected peripherally into the limb intramuscularly.  
     
     
         42 . The method of  claim 36 , wherein the autologous bone marrow has been stimulated.  
     
     
         43 . The method of  claim 42 , wherein the autologous bone marrow has been stimulated by contact with one or more cytokines or other proteins or stimulating agents.  
     
     
         44 . The method of  claim 42 , wherein the cytokines are selected from the group consisting of HIF-1, EPAS1, MCP-1, and CM-CSF.  
     
     
         45 . The method of  claim 42 , wherein the autologous bone marrow has been transfected with vectors carrying relevant genes.  
     
     
         46 . The method of  claim 45 , wherein the autologous bone marrow has been transfected with a plasmid vector or an adenoviral vector, or any other vector demonstrated to be effective for gene transfer, carrying the HIF-1 or EPAS1 transgene, or any other transgene demonstrated to be effective in enhancing the capacity of bone marrow to induce angiogenesis.  
     
     
         47 . The method of  claim 42 , wherein the autologous bone marrow has been stimulated by transient exposure to hypoxia or a form of energy.  
     
     
         48 . The method of  claim 42 , wherein conditioned medium derived from autologous bone marrow growing in culture is injected into the ischemic heart or limb.  
     
     
         49 . The method of  claim 36 , wherein the autologous bone marrow is administered in combination with a pharmacological drug, protein, or gene or any other compound or therapy that may enhance bone marrow production of angiogenic growth factors and/or promote endothelial cell proliferation, migration, or blood vessel formation.  
     
     
         50 . The method of  claim 49 , wherein the autologous bone marrow and the other agent or agents are administered together.  
     
     
         51 . The method of  claim 49 , wherein the autologous bone marrow and the other agent or agents are combined prior to administration.  
     
     
         52 . The method of  claim 51 , wherein the autologous bone marrow has been stimulated.  
     
     
         53 . A method of enhancing myocardial function in a patient with impaired myocardial function, which comprises the step of administering an effective amount of autologous bone marrow.  
     
     
         54 . The method of  claim 53 , wherein the autologous bone marrow is injected.  
     
     
         55 . The method of  claim 53 , wherein the autologous bone marrow is injected intramyocardially.  
     
     
         56 . The method of  claim 55 , wherein the autologous bone marrow is injected trans-epicardially or trans-endocardially.  
     
     
         57 . The method of  claim 56 , wherein with the trans-endocardial approach a catheter-based approach is used.  
     
     
         58 . The method of  claim 53 , wherein the autologous bone marrow is injected peripherally into the limb intramuscularly.  
     
     
         59 . The method of  claim 53 , wherein the autologous bone marrow has been stimulated.  
     
     
         60 . The method of  claim 59 , wherein the autologous bone marrow has been stimulated by contact with one or more cytokines or other proteins or stimulating agents.  
     
     
         61 . The method of  claim 59 , wherein the cytokines are selected from the group consisting of HIF-1, EPAS1, MCP-1, and CM-CSF.  
     
     
         62 . The method of  claim 59 , wherein the autologous bone marrow has been transfected with vectors carrying relevant genes.  
     
     
         63 . The method of  claim 62 , wherein the autologous bone marrow has been transfected with a plasmid vector or an adenoviral vector, or any other vector demonstrated to be effective for gene transfer, carrying the HIF-1 or EPAS1 transgene, or any other transgene demonstrated to be effective in enhancing the capacity of bone marrow to induce angiogenesis.  
     
     
         64 . The method of  claim 59 , wherein the autologous bone marrow has been stimulated by transient exposure to hypoxia or a form of energy.  
     
     
         65 . The method of  claim 59 , wherein conditioned medium derived from autologous bone marrow growing in culture is injected into the ischemic heart or limb.  
     
     
         66 . The method of  claim 53 , wherein the autologous bone marrow is administered in combination with a pharmacological drug, protein, or gene or any other compound or therapy that may enhance bone marrow production of angiogenic growth factors and/or promote endothelial cell proliferation, migration, or blood vessel formation.  
     
     
         67 . The method of  claim 66 , wherein the autologous bone marrow and the other agent or agents are administered together.  
     
     
         68 . The method of  claim 66 , wherein the autologous bone marrow and the other agent or agents are combined prior to administration.  
     
     
         69 . The method of  claim 68 , wherein the autologous bone marrow has been stimulated.  
     
     
         70 . A method of treating an atrial or ventricular condition in the heart of a patient, which comprises the step of administering an effective amount of autologous bone marrow.  
     
     
         71 . The method of  claim 70 , wherein the autologous bone marrow is injected.  
     
     
         72 . The method of  claim 70 , wherein the autologous bone marrow is injected intramyocardially.  
     
     
         73 . The method of  claim 72 , wherein the autologous bone marrow is injected trans-epicardially or trans-endocardially.  
     
     
         74 . The method of  claim 73 , wherein with the trans-endocardial approach a catheter-based approach is used.  
     
     
         75 . The method of  claim 70 , wherein the autologous bone marrow is injected peripherally into the limb intramuscularly.  
     
     
         76 . The method of  claim 70 , wherein the autologous bone marrow has been stimulated.  
     
     
         77 . The method-of  claim 76 , wherein the autologous bone marrow has been stimulated by contact with one or more cytokines or other proteins or stimulating agents.  
     
     
         78 . The method of  claim 76 , wherein the cytokines are selected from the group consisting of HIF-1, EPAS1, MCP-1, and CM-CSF.  
     
     
         79 . The method of  claim 76 , wherein the autologous bone marrowhas been transfected with vectors carrying relevant genes.  
     
     
         80 . The method of  claim 79 , wherein the autologous bone marrow has been transfected with a plasmid vector or an adenoviral vector, or any other vector demonstrated to be effective for gene transfer, carrying the HIF-1 or EPAS1 transgene, or any other transgene demonstrated to be effective in enhancing the capacity of bone marrow to induce angiogenesis.  
     
     
         81 . The method of  claim 76 , wherein the autologous bone marrow has been stimulated by transient exposure to hypoxia or a form of energy.  
     
     
         82 . The method of  claim 76 , wherein conditioned medium derived from autologous bone marrow growing in culture is injected into the ischemic heart or limb.  
     
     
         83 . The method of  claim 70 , wherein the autologous bone marrow is administered in combination with a pharmacological drug, protein, or gene or any other compound or therapy that may enhance bone marrow production of angiogenic growth factors and/or promote endothelial cell proliferation or migration, or blood vessel formation.  
     
     
         84 . The method of  claim 83 , wherein the autologous bone marrow and the other agent or agents are administered together.  
     
     
         85 . The method of  claim 83 , wherein the autologous bone marrow and the other agent or agents are combined prior to administration.  
     
     
         86 . The method of  claim 85 , wherein the autologous bone marrow has been stimulated.  
     
     
         87 . A composition for the treatment of a cardiac or myocardial condition, which comprises an effective amount of autologous bone marrow, wherein the cardiac or myocardial condition is treated.  
     
     
         88 . The composition of  claim 87 , wherein the autologous bone marrow has been stimulated.  
     
     
         89 . The composition of  claim 88 , wherein the autologous bone marrow has been stimulated by contact with one or more cytokines or other proteins or stimulating agents.  
     
     
         90 . The composition of  claim 89 , wherein the cytokines are selected from the group consisting of HIF-1, EPAS1, MCP-1, and CM-CSF.  
     
     
         91 . The composition of  claim 88 , wherein the autologous bone marrow has been transfected with vectors carrying relevant genes.  
     
     
         92 . The composition of  claim 91 , wherein the autologous bone marrow has been transfected with a plasmid vector or an adenoviral vector, or any other vector demonstrated to be effective for gene transfer, carrying the HIF-1 or EPAS1 transgene, or any other transgene demonstrated to be effective in enhancing the capacity of bone marrow to induce angiogenesis.  
     
     
         93 . The composition of  claim 89 , wherein the autologous bone marrow has been stimulated by exposure to hypoxia.  
     
     
         94 . The composition of  claim 89 , wherein conditioned medium derived from autologous bone marrow growing in culture is injected into the ischemic heart or limb.  
     
     
         95 . The composition of  claim 87 , wherein the autologous bone marrow is administered in combination with a pharmacological drug, protein, or gene or any other compound or therapy that may enhance bone marrow production of angiogenic growth factors and/or promote endothelial cell proliferation, migration, or blood vessel formation.  
     
     
         96 . The composition of  claim 87  which comprises heparin or another anticoagulent.  
     
     
         97 . The composition of  claim 87  for enhancing collateral blood vessel formation.  
     
     
         98 . The composition of  claim 87  for promoting the development of newly implanted myocardial cells.  
     
     
         99 . The composition of  claim 87  for improving the electrical conductivity of the heart of a patient with cardiac electrical pathway impairment.  
     
     
         100 . The composition of  claim 87  for enhancing the myocardial function in a patient with impaired myocardial function.  
     
     
         101 . The composition of  claim 87  for treating a left or right ventricular condition causing impaired heart function in the heart of a patient.  
     
     
         102 . The composition of  claim 87  for affecting the contractility of a patient's heart.