Cardiac stem cells for cardiac repair

Abstract

Embodiments of the disclosure concern compositions and methods of use related to particular c-kit+ mesenchymal cells, including cardiac stem cells, obtained from a pediatric or neonatal individual. In specific embodiments, the cells, or conditioned medium or partial or total secretomes thereof, are provided in an effective amount to an individual in need thereof.

1 . As a composition of matter, a pharmaceutical composition comprising an isolated plurality of human cardiac cells that have two or more of the following characteristics: ckit+, CD90+, CD105+, CD31−, CD34−, CD45−, and tryptase negative; and a pharmaceutically acceptable carrier. 
     
     
         2 . The composition of  claim 1  wherein the cells have one, two, three, or more of the following characteristics: GATA4+, CD44+, CD140−, CD106−, tryptase−, CD80−, CD86−, HLA Class I+, and HLA Class II−. 
     
     
         3 . The composition of  claim 1 , wherein the cells are isolated from the heart of a neonatal individual. 
     
     
         4 . The composition of  claim 1 , wherein the cells are isolated from the heart of a pediatric individual. 
     
     
         5 . The composition of  claim 1 , wherein the individual has a cardiac medical condition. 
     
     
         6 . The composition of  claim 1 , wherein the individual has normal myocardium. 
     
     
         7 . The composition of  claim 1 , wherein the cells are from the myocardium of a pediatric individual with end stage heart failure. 
     
     
         8 . The composition of  claim 1 , wherein the cells are from the myocardium of a neonatal individual with congenital heart disease. 
     
     
         9 . The composition of  claim 1 , wherein the cells secrete exosomes that are CD63+. 
     
     
         10 . The composition of  claim 1 , wherein the cells secrete one or more cytokines. 
     
     
         11 . The composition of  claim 1 , wherein the cells secrete one or more pro-angiogenic factors. 
     
     
         12 . The composition of  claim 1 , wherein the cells secrete one or more VEGF-A, HGF, SCF, SDF-1α, and ANG-1. 
     
     
         13 . The composition of  claim 1 , wherein the cells express VEGF-A and SDF-1α. 
     
     
         14 . The composition of  claim 1 , wherein the cells have activation of expression of one or more components of the heat shock response. 
     
     
         15 . The composition of  claim 1 , wherein the cells have activation of expression of HSF-1, HSP60, and/or HSP70. 
     
     
         16 . The composition of  claim 1 , wherein the cells are manipulated to express Hsp70, Hsp27, ISL-1, or a combination thereof. 
     
     
         17 . The composition of  claim 1 , wherein the cells are manipulated to increase secretion of SDF-1α, VEGF-A, PGDF-A, IL-6, FGF-2, or a combination thereof. 
     
     
         18 . The composition of  claim 1 , wherein the cells are suspended in a medium comprising one or more heat shock response inducers. 
     
     
         19 . The composition of  claim 18 , wherein the one or more heat shock response inducers are selected from the group consisting of celastrol, triptolide, and a combination thereof. 
     
     
         20 . A method of treating an individual for a cardiac medical condition, comprising the step of providing to the individual a therapeutically effective amount of the composition of  claim 1 , medium conditioned by the composition of  claim 1 , exosomes secreted by the composition of  claim 1 , or a combination thereof. 
     
     
         21 . The method of  claim 20 , wherein the composition, medium, exosomes, or a combination thereof are provided to an hypoxic environment in the heart of the individual. 
     
     
         22 . The method of  claim 20 , wherein the cardiac medical condition is heart failure, cardiomyopathy, or congenital heart disease. 
     
     
         23 . A conditioned medium from the cells of  claim 1 . 
     
     
         24 . Exosomes from the cells of  claim 1 .