Compositions and Methods for Treatment of Cardiovascular Disorders

Abstract

Methods for treating cardiovascular disorders that include administration of an ECM based composition to damaged cardiovascular tissue in conjunction with a treatment remedy, such as transmyocardial revascularization (TMR), which induces enhanced bioremodeling of the damaged cardiovascular tissue and regeneration of new cardiovascular tissue and associated structures with site-specific structural and functional properties.

What is claimed is: 
     
         1 . A method for treating damaged cardiovascular tissue of a subject, the method comprising the steps of:
 providing a mixed gel extracellular matrix (ECM) composition, said ECM composition comprising acellular ECM from a mammalian tissue source,   said acellular ECM adapted to induce a first level of stem cell migration, stern cell proliferation, angiogenesis, and bioremodeling of said damaged cardiovascular tissue, and regeneration of new cardiovascular tissue, when said acellular ECM is delivered to said damaged cardiovascular tissue;   providing a transmyocardial revascularization (TMR) device, said TMR device adapted to generate laser energy and transmit said laser energy to a target cardiovascular tissue region disposed proximate said damaged cardiovascular tissue, wherein an inciting event is induced in said target cardiovascular tissue region and a TMR energy impact region is formed proximate said damaged cardiovascular tissue, whereby a second level of stem cell migration, stem cell proliferation and angiogenesis of said damaged cardiovascular tissue is induced; and   delivering said ECM composition to said damaged cardiovascular tissue in conjunction with directing first laser energy to a first target cardiovascular tissue region disposed proximate said damaged cardiovascular tissue with said TMR device, wherein a first inciting event is induced in said target cardiovascular tissue region and a first TMR energy impact region is formed proximate said damaged cardiovascular tissue,   said ECM composition and first inciting event jointly inducing a third level of stem cell migration, stem cell proliferation, angiogenesis of said damaged cardiovascular tissue, whereby a second level of bioremodeling of said damaged cardiovascular tissue and regeneration of new cardiovascular tissue is induced, said second level of bioremodeling of said damaged cardiovascular tissue and regeneration of new cardiovascular tissue being greater than said first level of bioremodeling of said damaged cardiovascular tissue and regeneration of new cardiovascular tissue.   
     
     
         2 . The method of  claim 1 , wherein said damaged cardiovascular tissue comprises ischemic infarct tissue. 
     
     
         3 . The method of  claim 1 , wherein said first energy impact region is disposed at a distance of 1 mm to 30 mm from said damaged cardiovascular tissue. 
     
     
         4 . The method of  claim 1 , wherein said laser energy comprises an energy flux in the range of 50-500 Joule/mm 2 . 
     
     
         5 . The method of  claim 1 , wherein said laser energy is delivered to said target cardiovascular tissue via a plurality of laser pulses comprising a pulse frequency in the range of 5-25 Hz. 
     
     
         6 . The method of  claim 1 , wherein said acellular ECM comprises ECM from decellularized mammalian tissue selected from the group consisting of small intestine submucosa, urinary bladder submucosa, stomach submucosa, amniotic membrane and Wharton's jelly. 
     
     
         7 . The method of  claim 1 , wherein said ECM composition further comprises exogenously added exosomes. 
     
     
         8 . The method of  claim 7 , wherein said exosomes comprise mesenchymal stem cell (MSC) derived exosomes. 
     
     
         9 . The method of  claim 7 , wherein said exogenously added exosomes comprise an encapsulated growth factor selected from the group consisting of exogenous basic fibroblast growth factor (bFGF), transforming growth factor beta (TGF-β) and vascular endothelial growth factor (VEGF). 
     
     
         10 . The method of  claim 7 , wherein said exogenously added exosomes comprise an encapsulated inflammation modulating agent selected from the group consisting of a cytokine, transcription factor RNA and micro RNA (miRNA).