Methods of improving cell-based therapy

Abstract

Provided are methods for improving cell-based therapies by co-administration with an agent that increases the production and or levels of epoxygenated fatty acids, as well as kits, stents and patches for co-administering stem cells with an agent that increases the production and/or levels of epoxygenated fatty acids.

1 . A method of increasing, improving and/or promoting the survival, engraftment, and/or integration of transplanted stem cells in a tissue of a subject in need thereof, comprising co-administering to the subject the stem cells with an agent that increases the production and/or level of epoxygenated fatty acids. 
     
     
         2 . A method of reversing, mitigating and/or improving one or more symptoms associated with cardiomyopathy or cardiac arrhythmia in an subject in need thereof, said method comprising co-administering to said subject a population of stem cells and an agent that increases the production and/or level of epoxygenated fatty acids. 
     
     
         3 . The method of  claim 1 , wherein the subject has cardiomyopathy, and wherein the cardiomyopathy is one or more of hypertrophic cardiomyopathy, hypertensive cardiomyopathy, diabetic cardiomyopathy and dilated cardiomyopathy. 
     
     
         4 . (canceled) 
     
     
         5 . The method of  claim 2 , wherein said cardiomyopathy is due to or secondary to one or more of valvular heart disease, myocardial infarction, and familial hypertrophic cardiomyopathy, and wherein said valvular heart disease is secondary to rheumatic fever, myxomatous degeneration of the valve, or papillary muscle dysfunction. 
     
     
         6 . (canceled) 
     
     
         7 . The method of  claim 2 , wherein the cardiomyopathy is dilated cardiomyopathy, and wherein said dilated cardiomyopathy is one or more of alcohol-induced cardiomyopathy, viral-induced cardiomyopathy, familial dilated cardiomyopathy and dilated cardiomyopathy is caused by administration of an anti-cancer drug or exposure to a toxic agent. 
     
     
         8 . (canceled) 
     
     
         9 . The method of  claim 2 , wherein the administration of said stem cells and said agent or agents inhibits cardiac arrhythmia, wherein the cardiac arrhythmia is one or more of atrial fibrillation, atrial flutter, ventricular fibrillation and ventricular tachycardia. 
     
     
         10 . (canceled) 
     
     
         11 . The method of  claim 1 , wherein the agent comprises one or more epoxygenated fatty acids. 
     
     
         12 . The method of  claim 1 , wherein the epoxygenated fatty acids are selected from the group consisting of cis-epoxyeicosantrienoic acids (“EETs”), epoxides of linoleic acid, epoxides of eicosapentaenoic acid (“EPA”), epoxides of docosahexaenoic acid (“DHA”), epoxides of the arachidonic acid (“AA”), epoxides of cis-7,10,13,16,19-docosapentaenoic acid, and mixtures thereof. 
     
     
         13 . (canceled) 
     
     
         14 . A method of  claim 1 , wherein the agent is an inhibitor of soluble epoxide hydrolase (“sEH”). 
     
     
         15 . The method of  claim 14 , wherein the inhibitor of sEH comprises a primary pharmacophore selected from the group consisting of a urea, a carbamate, and an amide. 
     
     
         16 - 19 . (canceled) 
     
     
         20 . The method of  claim 14 , wherein the inhibitor of sEH has an 1050 of less than about 100 μM. 
     
     
         21 - 26 . (canceled) 
     
     
         27 . The method of  claim 1 , wherein the subject is a human. 
     
     
         28 . The method of  claim 1 , wherein the stem cells are selected from multipotent stem cells, pluripotent stem cells, and induced pluripotent stem cells. 
     
     
         29 . The method of  claim 1 , wherein the stem cells comprise mesenchymal stem cells, myocyte stem cells and/or cardiomyocyte stem cells. 
     
     
         30 - 31 . (canceled) 
     
     
         32 . The method of  claim 1 , wherein the stem cells are selected from the group consisting of cardiomyocytes or cardiac progenitor cells derived from multipotent stem cells, cardiomyocytes or cardiac progenitor cells derived from pluripotent stem cells, cardiomyocytes or cardiac progenitor cells derived from induced pluripotent stem cells, adult cardiac progenitor cells and cardiac stem cells, and wherein the stem cells comprise adult cardiac stem cells or cardiac progenitor cells derived from human cardiac tissues. 
     
     
         33 . (canceled) 
     
     
         34 . The method of  claim 1 , wherein the stem cells are syngeneic, allogeneic or xenogeneic to the subject. 
     
     
         35 - 37 . (canceled) 
     
     
         38 . The method of  claim 1 , wherein the stem cells are administered intravenously, intra-arterially or intralesionally. 
     
     
         39 . (canceled) 
     
     
         40 . The method of  claim 1 , wherein the stem cells and the agent that increases the production and/or level of epoxygenated fatty acids are administered by different routes of administration. 
     
     
         41 . The method of  claim 14 , wherein the stem cells and the inhibitor of sEH are concurrently co-administered. 
     
     
         42 . The method of  claim 14 , wherein the stem cells and the inhibitor of sEH are sequentially co-administered. 
     
     
         43 . The method of  claim 1 , wherein the tissue is cardiac tissue. 
     
     
         44 . (canceled) 
     
     
         45 . A stent comprising a population of stem cells and one or more agents that increase the production and/or level of epoxygenated fatty acids. 
     
     
         46 . (canceled) 
     
     
         47 . A patch comprising a population of stem cells and one or more agents that increase the production and/or level of epoxygenated fatty acids. 
     
     
         48 - 69 . (canceled)