Cdc-derived exosomes for treatment of ventricular tachyarrythmias

Abstract

Described herein are compositions and methods related to use of exosomes, including cardiosphere derived cell (CDC)-derived exosomes for treatment and prevention of heart related disease and conditions, such as ventral arrhythmias, such as tachycardias. CDC-derived exosomes delivered by endocardial injection can diminish the total amount of isolated late potentials associated with an isthmus of slow conduction, while reducing the isoelectric interval between late abnormal ventricular activity and decreasing the incidence of inducible ventricular arrhythmias, thereby providing a biological treatment for arrhythmias which otherwise requires therapeutic interventions with adverse effects.

1 . A method of improving cardiac performance in a subject, comprising:
 injecting a therapeutically effective amount of a composition comprising exosomes into a myocardium of a subject afflicted with scarred myocardium, thereby treating the subject,   wherein the exosomes are obtained from human cardiosphere-derived cells (CDCs).   
     
     
         2 . The method of  claim 1 , wherein the subject is afflicted with abnormal electrical activity in the heart. 
     
     
         3 . The method of  claim 1 , wherein the subject is afflicted with slow zones of conduction in the heart. 
     
     
         4 . The method of  claim 1 , wherein the subject suffers from ventricular tachycardia. 
     
     
         5 . The method of  claim 1 , wherein the subject has had a myocardial infarction. 
     
     
         6 . The method of  claim 1 , wherein the subject has an implantable cardioverter-defibrillator (ICD). 
     
     
         7 . The method of  claim 1 , wherein administering a composition comprises focal delivery at a site of isolated late potentials. 
     
     
         8 . The method of  claim 1 , wherein the composition comprising exosomes comprises 3.75 mg/mL of said exosomes in aqueous media. 
     
     
         9 . The method of  claim 8 , wherein the aqueous media is Iscove Modified Dulbecco Media (IMDM). 
     
     
         10 . The method of  claim 8 , wherein the composition is delivered to the subject in 6-8 injections of 250 μL-330 μL. 
     
     
         11 . The method of  claim 10 , wherein the injections are made into an infarct zone and into a penumbra of the infarct zone of the myocardium. 
     
     
         12 . A pharmaceutical composition comprising:
 extracellular vesicles obtained from human cardiosphere-derived cells (CDCs); and   Iscove Modified Dulbecco Media (IMDM).   
     
     
         13 . The pharmaceutical composition of  claim 12 , wherein the extracellular vesicles are present at a concentration of 3.75 mg/mL. 
     
     
         14 . The pharmaceutical composition of  claim 12 , wherein the extracellular vesicles are exosomes. 
     
     
         15 . The pharmaceutical composition of  claim 12 , wherein the composition does not comprise cells. 
     
     
         16 . A method of treating ventricular tachycardia in a subject, comprising:
 identifying localized areas of late potentials in a myocardium of the subject;   injecting a therapeutically effective amount of a composition comprising exosomes into the myocardium of the localized areas, thereby treating the subject,   wherein the exosomes are obtained from human cardiosphere-derived cells (CDCs)   
     
     
         17 . The method of  claim 16 , wherein the subject has an implantable cardioverter-defibrillator (ICD). 
     
     
         18 . The method of  claim 16 , wherein the myocardium of the subject comprises scar tissue. 
     
     
         19 . The method of  claim 16 , wherein the subject has had a myocardial infarction. 
     
     
         20 . The method of  claim 16 , wherein the composition is delivered to the subject in 6-8 injections of 250 μL-330 μL.