Bone marrow derived cd271 precursor cells for cardiac repair

Abstract

Methods for the isolation of CD271 + stem cell populations are important in the prevention or treatment of cardiovascular diseases and repair of cardiac tissue. The methods are applicable to stem cells from different sources and can be used to treat or prevent diseases or repair of tissues elsewhere in the organism's body.

1 . A method of preventing or treating a cardiovascular disease or disorder in a patient comprising:
 isolating CD271 +  mesenchymal stem cell precursors from bone marrow of a subject, wherein the subject is the same or different than the patient;   administering to the patient a therapeutically effective amount of isolated CD271 +  mesenchymal stem cell precursors; and,   preventing or treating the cardiovascular disease or disorder in the patient.   
     
     
         2 . The method of  claim 1 , wherein the CD271 +  mesenchymal stem cell precursors are isolated from bone marrow cells having a low affinity nerve growth receptor (NGFR; CD271). 
     
     
         3 . The method of  claim 1 , wherein the CD271 +  mesenchymal stem cell precursors are isolated from donors comprising: autologous, syngeneic, allogeneic, or xenogeneic. 
     
     
         4 . The method of  claim 1 , wherein the CD271 +  mesenchymal stem cell precursors differentiate into myocytes, cardiomyocytes, endothelial cells, myocardial cells, epicardial cells, vascular endothelial cells, or smooth muscle cells after administration to the patient. 
     
     
         5 . The method of  claim 1 , wherein the CD271 +  mesenchymal stem cell precursors differentiate into lineages comprising: myocardial, vascular, or endothelial lineages after administration to the patient. 
     
     
         6 . The method of  claim 4 , wherein the cardiomyocytes are identified by markers comprising: GATA-4, Nkx2.5 or α-sarcomeric actin. 
     
     
         7 . The method of  claim 4 , wherein the smooth muscle cells are identified by markers comprising: α-smooth muscle actin or SMA22. 
     
     
         8 . The method of  claim 4 , wherein the endothelial cells are identified by markers comprising: CD31 or vimentin. 
     
     
         9 . The method of  claim 1 , wherein one or more agents are administered to the patient with the CD271 +  mesenchymal stem cell precursors, the agents comprising at least one of: cytokines, chemotactic factors, growth factors, or differentiation factors. 
     
     
         10 . The method of  claim 1 , wherein the cardiovascular disease or disorder comprises: heart failure, atherosclerosis, ischemia, myocardial infarction, transplantation, hypertension, restenosis, angina pectoris, rheumatic heart disease, congenital cardiovascular defect, ischemic cardiomyopathy, or age-related cardiomyopathy. 
     
     
         11 . The method of  claim 1 , wherein the CD271 +  mesenchymal stem cell precursors are administered to the patient in varying concentrations over a period of time. 
     
     
         12 . The method of  claim 1 , wherein the CD271 +  mesenchymal stem cell precursors engraft in the heart of the patient in infarct and border zones. 
     
     
         13 . The method of  claim 1 , wherein the CD271 +  mesenchymal stem cell precursors are conditioned with media conditioned by heart derived stromal cells before administration to the patient. 
     
     
         14 . The method of  claim 1 , wherein the CD271 +  mesenchymal stem cell precursors are cultured ex vivo before administration to the patient. 
     
     
         15 . The method of  claim 1 , wherein freshly isolated CD271 +  mesenchymal stem cell precursors are administered to the patient. 
     
     
         16 . The method of  claim 4 , wherein the myocytes are identified by markers comprising: troponin I, α-sarcomeric actin, cardiac myocyte, desmin, α-cardiac actinin, connexin-43, GATA-4, Nkx-2.5, or MEF2.