Treatment of heart disease

Abstract

Disclosed herein are methods, compositions and kits for treating cardiac stem cells to be administered to a subject in need thereof, e.g., with a damaged myocardium. The methods, composition and kits of the invention can be used to treat cardiovascular diseases such as heart failure, myocardial infarction and an age-related cardiomyopathy.

1 . A method of treating cardiac stem cells to be administered to a subject in need thereof, comprising:
 a. contacting a population of cardiac stem cells with an effective amount of IGF-2 or a variant thereof;   b. administering the population of cardiac stem cells from step (a) to the subject in need thereof.   
     
     
         2 . The method of  claim 1 , wherein at least a subset of the population of cardiac stem cells express IGF-1 receptor. 
     
     
         3 . The method of  claim 1 , wherein the population of cardiac stem cells is administered to an area of a damaged heart tissue of the subject in need thereof. 
     
     
         4 . The method of  claim 1 , wherein the population of cardiac stem cells is administered by injection, by a catheter, or via an intracoronary route. 
     
     
         5 . (canceled) 
     
     
         6 . (canceled) 
     
     
         7 . The method  claim 1 , wherein the effective amount of IGF-2 or a variant thereof is sufficient to increase expression of at least one marker for myocyte differentiation by at least about 10%, as compared to cardiac stem cells in the absence of IGF-2 or a variant thereof. 
     
     
         8 . The method of  claim 7 , wherein the marker for myocyte differentiation is selected from the group consisting of: α-sarcomeric actin, connexin-43, Nkx2.5, GATA-4 and MEF2C. 
     
     
         9 . The method of  claim 1 , wherein the effective amount of IGF-2 or a variant thereof is about 100 ng/mL. 
     
     
         10 . The method of  claim 1 , wherein the cardiac stem cells are contacted with IGF-2 or a variant thereof for an amount of time sufficient to increase myocyte formation, as compared to cardiac stem cells in the absence of IGF-2; or an amount of time sufficient for the cardiac stem cells to confer acquisition of at least one adult cardiomyocyte phenotype, as compared to cardiac stem cells in the absence of IGF-2. 
     
     
         11 . (canceled) 
     
     
         12 . The method of  claim 10 , wherein the adult cardiomyocyte phenotype is selected from the group consisting of: a myocyte volume greater than 2000 μm 3 , contractility in response to electric stimulation, an elongated morphology, calcium tolerance, expression of at least one contractile protein, and activation of ion current channels. 
     
     
         13 . The method of  claim 12 , wherein the contractile protein is selected from the group consisting of: α-sarcomeric actin, myosin heavy chains, myosin light chains and tropomyosin. 
     
     
         14 . The method of  claim 1 , wherein the cardiac stem cells are contacted with IGF-2 or a variant thereof for about 2 hours. 
     
     
         15 . The method of  claim 1 , wherein the subject in need thereof has a damaged myocardium, or is diagnosed with or suffering from a myocardial infarction, a heart failure or an age-related cardiomyopathy. 
     
     
         16 . (canceled) 
     
     
         17 . (canceled) 
     
     
         18 . (canceled) 
     
     
         19 . (canceled) 
     
     
         20 . (canceled) 
     
     
         21 . The method of  claim 1 , wherein the cardiac stem cells are isolated from a myocardial tissue of the subject. 
     
     
         22 . The method of  claim 1 , further comprising:
 contacting the population of cardiac stem cells with an effective amount of IGF-1 or a variant thereof prior to   said contacting the population of cardiac stem cells with the effective amount of IGF-2 or a variant thereof.   
     
     
         23 . (canceled) 
     
     
         24 . The method of  claim 22 , wherein the effective amount of IGF-1 or a variant thereof is sufficient to increase proliferation of the cardiac stem cells by at least about 10%, as compared to cardiac stem cells in the absence of IGF-1. 
     
     
         25 . The method of  claim 22 , wherein the effective amount of IGF-1 or a variant thereof is about 100 ng/mL. 
     
     
         26 . The method of  claim 22 , wherein the cardiac stem cells are contacted with IGF-1 for at least about 12 hours. 
     
     
         27 . (canceled) 
     
     
         28 . (canceled) 
     
     
         29 . (canceled) 
     
     
         30 . (canceled) 
     
     
         31 . (canceled) 
     
     
         32 . (canceled) 
     
     
         33 . (canceled) 
     
     
         34 . (canceled) 
     
     
         35 . (canceled) 
     
     
         36 . (canceled) 
     
     
         37 . (canceled) 
     
     
         38 . (canceled) 
     
     
         39 . (canceled) 
     
     
         40 . (canceled) 
     
     
         41 . (canceled) 
     
     
         42 . (canceled) 
     
     
         43 . (canceled) 
     
     
         44 . (canceled) 
     
     
         45 . A composition comprising at least one cardiac stem cell and an effective amount of IGF-2 or a variant thereof. 
     
     
         46 . The composition of  claim 45 , further comprising a pharmaceutically acceptable carrier, or a cell culture medium. 
     
     
         47 . (canceled) 
     
     
         48 . The composition of  claim 45 , wherein at least one cardiac stem cell expresses IGF-1 receptor. 
     
     
         49 . The composition of  claim 45 , wherein the effective amount of IGF-2 or a variant thereof is sufficient to increase expression of at least one marker for myocyte differentiation by at least about 10%, as compared to cardiac stem cells in the absence of IGF-2. 
     
     
         50 . (canceled) 
     
     
         51 . The composition of  claim 45 , wherein the effective amount of IGF-2 or a variant thereof is about 100 ng/mL. 
     
     
         52 . The composition of  claim 45 , wherein the cardiac stem cell is isolated from a myocardial tissue of a subject. 
     
     
         53 . The composition of  claim 45 , further comprising an effective amount of IGF-1, or a variant thereof. 
     
     
         54 . (canceled) 
     
     
         55 . (canceled) 
     
     
         56 . (canceled) 
     
     
         57 . The composition of  claim 53 , wherein the effective amount of IGF-1 or a variant thereof is sufficient to increase proliferation of the cardiac stem cells by at least about 10%, as compared to cardiac stem cells in the absence of IGF-1. 
     
     
         58 . (canceled) 
     
     
         59 . (canceled) 
     
     
         60 . (canceled) 
     
     
         61 . (canceled) 
     
     
         62 . (canceled) 
     
     
         63 . The composition of  claim 45 , wherein the composition is used for administration to a subject in need thereof. 
     
     
         64 . The composition of  claim 63 , wherein the subject in need thereof has a damaged myocardium, or is diagnosed with or suffering from a myocardial infarction, a heart failure, or an age-related cardiomyopathy. 
     
     
         65 . (canceled) 
     
     
         66 . (canceled) 
     
     
         67 . (canceled) 
     
     
         68 . (canceled) 
     
     
         69 . (canceled) 
     
     
         70 . (canceled) 
     
     
         71 . The composition of  claim 45 , wherein the composition is injectable. 
     
     
         72 . (canceled) 
     
     
         73 . (canceled)