Methods of cardiac repair

Abstract

Provided herein is a new method to isolate and expand cardiac progenitor/stem cells from a placenta, which produces a cell population enriched in multipotent functional progenitor/stem cells. Cardiac progenitor/stem cells isolated by this method maintain their self-renewal character in vitro and differentiate into normal cells in myocardium, including cardiomyocytes, endothelial cells, and smooth muscle cells, after transplantation into ischemic hearts. Also provided in this application are substantially pure populations of multipotent cardiac progenitor/stem cells, and their use to treat and prevent diseases and injuries, including those resulting from myocardial infarction. A model for assessing the potential of cardiac stem cells for treatment of myocardial infarction is also provided.

1 . A composition comprising a population of cells and a pharmaceutically acceptable carrier for increasing cardiomyocyte formation, increase cardiomyocyte proliferation, increase cardiomyocyte cell cycle activation, increase mitotic index of cardiomyocytes, increase myofilament density, increase borderzone wall thickness, or a combination thereof, wherein said cells express one or more markers identified in Table 2 or in  FIG. 5C . 
     
     
         2 . The composition of  claim 1 , wherein said cells are derived from placenta. 
     
     
         3 . The composition of  claim 1 , wherein said cells are progenitor cells or stem cells. 
     
     
         4 . The composition of  claim 1 , wherein said cells express Cdx2, Cd9, Eomes, CD34, CD31, c-kit or a combination thereof. 
     
     
         5 . A composition comprising a population of cells and a pharmaceutically acceptable carrier for treating myocardial infarction, chronic coronary ischemia, arteriosclerosis, congestive heart failure, dilated cardiomyopathy, restenosis, coronary artery disease, heart failure, arrhythmia, angina, atherosclerosis, hypertension, or myocardial hypertrophy, wherein said cells express one or more markers identified in Table 2 or in  FIG. 5C . 
     
     
         6 . The composition of  claim 5 , wherein said cells are derived from placenta. 
     
     
         7 . The composition of  claim 5 , wherein said cells are progenitor cells or stem cells. 
     
     
         8 . The composition of  claim 5 , wherein said cells express Cdx2, Cd9, Eomes, CD34, CD31, c-kit or a combination thereof. 
     
     
         9 - 27 . (canceled) 
     
     
         28 . A method of inducing cardiomyocyte regeneration, cardiac repair, vasculogenesis or cardiomyocyte differentiation, comprising contacting cells with injured heart tissue, wherein said cells express one or more markers identified in Table 2 or in  FIG. 5C . 
     
     
         29 . The method of  claim 28 , wherein said cells are derived from placenta. 
     
     
         30 . The method of  claim 28 , wherein said cells are progenitor cells or stem cells. 
     
     
         31 . The method of  claim 28 , wherein said cells express Cdx2, Cd9, Eomes, CD34, CD31, c-kit or a combination thereof. 
     
     
         32 . The method of  claim 28 , wherein the composition increases cardiomyocyte formation, increase cardiomyocyte proliferation, increase cardiomyocyte cell cycle activation, increase mitotic index of cardiomyocytes, increase myofilament density, increase borderzone wall thickness, or a combination thereof. 
     
     
         33 . The method of  claim 31 , wherein said Cdx2 cells are fetal stem cells 
     
     
         34 . The method of  claim 31 , wherein the Cdx2 cells are isolated cells. 
     
     
         35 . The method of  claim 28 , wherein the subject is diagnosed with, or at risk for, myocardial infarction, chronic coronary ischemia, arteriosclerosis, congestive heart failure, dilated cardiomyopathy, restenosis, coronary artery disease, heart failure, arrhythmia, angina, atherosclerosis, hypertension, or myocardial hypertrophy. 
     
     
         36 . The method of  claim 28 , wherein introducing or contacting the composition comprises implanting the composition into cardiac tissue of the subject, or wherein introducing or contacting the composition comprises injecting the composition into the subject. 
     
     
         37 . (canceled) 
     
     
         38 . The method of  claim 36 , wherein the cardiac tissue is selected from the group consisting of myocardium, endocardium, epicardium, connective tissue in the heart, and nervous tissue in the heart. 
     
     
         39 . The method of  claim 28 , wherein the amount of composition comprises from about 1×10 8  to about 1×10 2  cells. 
     
     
         40 . The method of  claim 28 , wherein the amount of introduced composition comprises from about 1×10 6  to about 1×10 5  cells.