Cardiac muscle repair or regeneration using bone marrow-derived stem cells

Abstract

Disclosed are compositions and methods for repairing and/or regenerating cardiac tissue by administering adult bone marrow-derived stem cells to an individual. These cells can be administered as a liquid injectible or as a preparation of cells in a matrix which is or becomes solid or semi-solid. The cells can be genetically modified to enhance myocardial differentiation and integration. Also disclosed is a method for replacing cells ex vivo in a heart valve for implantation.

1 . A cell preparation comprising adult bone marrow-derived stem cells in a dose effective to augment ventricular function in the heart of a subject in need thereof. 
     
     
         2 . The cell preparation of  claim 1 , wherein the stem cells are capable of differentiating into at least one cell type of each of the endodermal, ectodermal, and mesodermal embryonic lineages. 
     
     
         3 . The cell preparation of  claim 1 , wherein the dose comprises about 0.02 to about 150 milliliters of a pharmaceutically acceptable liquid medium and wherein the stem cells are at a concentration of about 10 to about 40 million cells per milliliter. 
     
     
         4 . The cell preparation of  claim 1 , wherein the stem cells have an induced expression of at least one cardiac specific marker. 
     
     
         5 . The cell preparation of  claim 4 , wherein the at least one cardiac specific marker is myosin heavy chain, sarcoplasmic reticulum calcium ATPase, or connexin 43. 
     
     
         6 . The cell preparation of  claim 4 , wherein the induced expression of at least one cardiac specific marker results from (i) co-culturing the stem cells with cardiac cells, (ii) use of chemical fusigens to create heterokaryons of the stem cells with cardiomyocytes, (iii) incubating the stem cells with extracts of mammalian hearts, (iv) treatment of the stem cells with growth factors, differentiating agents, or both, (v) mechanical or electrical stimulation of the stem cells, or (vi) mechanical or electrical coupling of the stem cells with cardiomyocytes. 
     
     
         7 . The cell preparation of  claim 1 , wherein the subject is a myocardial infarction patient, an ischemic heart transplant patient, a congestive heart failure patient, or a coronary artery bypass graft patient. 
     
     
         8 . The cell preparation of  claim 1 , wherein the cell preparation is capable of improving ventricular ejection fraction in the subject. 
     
     
         9 . A method of improving left ventricular ejection fraction in a patient comprising the step of:
 administering to the patient adult bone marrow-derived stem cells in an amount effective to improve ventricular ejection fraction.   
     
     
         10 . The method of  claim 9 , wherein the stem cells are autologous to the patient. 
     
     
         11 . The method of  claim 9 , wherein the stem cells are administered intravenously or intraarterially. 
     
     
         12 . The method of  claim 9 , wherein the stem cell are administered directly to the heart. 
     
     
         13 . The method of  claim 9 , wherein the stem cells are mesenchymal stem cells. 
     
     
         14 . A method of treating a patient having myocardial infarction or congestive heart failure and having reduced cardiac function comprising the step of:
 administering to the patient adult bone marrow-derived stem cells in an amount effective to improve cardiac function.   
     
     
         15 . 
     
     
         16 . The method of  claim 14 , wherein the cells are autologous. 
     
     
         17 . The method of  claim 14 , wherein the stem cells are administered intravenously or intraarterially. 
     
     
         18 . The method of  claim 14 , wherein the stem cells are administered directly to the heart. 
     
     
         19 . The method of  claim 14 , further comprising the step of assessing cardiac function at a time after administering the stem cells, wherein the assessing comprises measuring at least one of left ventricular ejection fraction, ventricular end diastolic pressure, or ventricular wall motion. 
     
     
         20 . The method of  claim 14 , wherein the stem cells are mesenchymal stem cells. 
     
     
         21 . A method of augmenting ventricular function in a patient comprising the step of:
 administering to the heart of the patient a cell suspension, wherein the cell suspension comprises adult bone marrow-derived stem cells and a pharmaceutically acceptable liquid medium.   
     
     
         22 . The method of  claim 19 , wherein the patient has a left ventricular ejection fraction of less than about 40%. 
     
     
         23 . The method of  claim 19 , wherein the stem cells are mesenchymal stem cells.