Methods and compositions for the repair and/or regeneration of damaged myocardium

Abstract

Methods, compositions, and kits for repairing damaged myocardium and/or myocardial cells including the administration cytokines are disclosed and claimed. Methods and compositions for the development of large arteries and vessels are also disclosed and claimed. The present application also discloses and claims methods and media for the growth, expansion, and activation of human cardiac stem cells.

1 . A method for inducing the proliferation and/or differentiation of cardiac stem cells in a subject in need thereof comprising administering to the subject's heart an effective amount of stem cell factor (SCF), wherein the proliferation and/or differentiation of said cardiac stem cells resident in the subject's heart is induced following SCF administration. 
     
     
         2 . The method of  claim 1 , wherein said cardiac stem cells are c-kit positive. 
     
     
         3 . The method of  claim 1 , wherein said cardiac stem cells are negative for CD45. 
     
     
         4 . The method of  claim 1 , wherein said cardiac stem cells are negative for CD34. 
     
     
         5 . The method of  claim 1 , wherein SCF is administered by an intramyocardial injection. 
     
     
         6 . The method of  claim 5 , wherein said effective amount of SCF is administered in more than one injection. 
     
     
         7 . The method of  claim 6 , wherein said effective amount of SCF is administered as multiple separate injections. 
     
     
         8 . The method of  claim 1 , wherein the SCF is administered by a trans-epicardial or transendocardial injection. 
     
     
         9 . The method of  claim 1 , wherein the SCF is administered by a catheter system. 
     
     
         10 . The method of  claim 1 , wherein said effective amount of SCF is 50 μg/kg to 500 μg/kg. 
     
     
         11 . The method of  claim 1 , wherein the SCF is administered in amount sufficient to induce the resident cardiac stem cells to differentiate into myocytes, smooth muscle cells, and endothelial cells. 
     
     
         12 . The method of  claim 1 , wherein the SCF is administered by delivering a vector encoding SCF to the subject's heart. 
     
     
         13 . The method of  claim 12 , wherein the vector is a viral vector. 
     
     
         14 . The method of  claim 13 , wherein the viral vector is an adenoviral vector or a lentiviral vector. 
     
     
         15 . The method of  claim 1 , wherein the subject's heart comprises areas of weakness or scarring. 
     
     
         16 . The method of  claim 1 , wherein the subject's heart comprises damaged myocardium resulting from ischemia or infarction. 
     
     
         17 . A method of generating myocardium in a subject in need thereof comprising administering to the subject's heart an effective amount of SCF sufficient to induce the proliferation and differentiation of cardiac stem cells resident in the subject's heart, wherein said resident cardiac stem cells differentiate into myocytes, smooth muscle cells, and endothelial cells following SCF administration, thereby generating myocardium. 
     
     
         18 . The method of  claim 17 , wherein said cardiac stem cells are c-kit positive. 
     
     
         19 . The method of  claim 17 , wherein said cardiac stem cells are negative for CD45. 
     
     
         20 . The method of  claim 17 , wherein said cardiac stem cells are negative for CD34. 
     
     
         21 . The method of  claim 17 , wherein SCF is administered by an intramyocardial injection. 
     
     
         22 . The method of  claim 21 , wherein said effective amount of SCF is administered in more than one injection. 
     
     
         23 . The method of  claim 22 , wherein said effective amount of SCF is administered as multiple separate injections. 
     
     
         24 . The method of  claim 17 , wherein the SCF is administered by a trans-epicardial or transendocardial injection. 
     
     
         25 . The method of  claim 17 , wherein the SCF is administered by a catheter system. 
     
     
         26 . The method of  claim 17 , wherein said effective amount of SCF is 50 μg/kg to 500 μg/kg. 
     
     
         27 . The method of  claim 17 , wherein the SCF is administered by delivering a vector encoding SCF to the subject's heart. 
     
     
         28 . The method of  claim 27 , wherein the vector is a viral vector. 
     
     
         29 . The method of  claim 28 , wherein the viral vector is an adenoviral vector or a lentiviral vector. 
     
     
         30 . The method of  claim 17 , wherein the subject's heart comprises areas of weakness or scarring. 
     
     
         31 . The method of  claim 17 , wherein the subject's heart comprises damaged myocardium resulting from ischemia or infarction.