Compositions for Regenerating Defective or Absent Myocardium

Abstract

Compositions of the invention for regenerating defective or absent myocardium comprise an emulsified or injectable extracellular matrix composition. The composition may also include an extracellular matrix scaffold component of any formulation, and further include added cells, proteins, or other components to optimize the regenerative process and restore cardiac function.

What is claimed is: 
     
         1 . An injectable graft composition for myocardial tissue regeneration, said composition comprising acellular extracellular matrix (ECM) from a mammalian tissue source comprising small intestine submucosa (SIS), said ECM comprising endogenous matrix metalloproteases (MMPs), transforming growth factor-beta (TGF-β), fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor (VEGF), said ECM further comprising an exogenously added supplemental bioactive component comprising fibronectin, said supplemental fibronectin comprising at least 0.1% by weight of said composition,
 said supplemental fibronectin being linked to said ECM, wherein said supplemental fibronectin attracts, links to and interacts with endogenous stem cells, fibroblasts and endothelial cells in vivo to control and enhance matrix formation and remodeling when said composition is administered to damaged cardiovascular tissue. 
 
     
     
         2 . The composition of  claim 1 , wherein said ECM further comprises an exogenously added cytokine. 
     
     
         3 . An injectable graft composition for myocardial tissue regeneration, said composition comprising acellular extracellular matrix (ECM) from a mammalian tissue source comprising liver basement submucosa (LBS), said ECM comprising endogenous matrix metalloproteases (MMPs), transforming growth factor-beta (TGF-β), fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor (VEGF), said ECM further comprising an exogenously added supplemental bioactive component comprising fibronectin, said supplemental fibronectin comprising at least 0.1% by weight of said composition,
 said supplemental fibronectin being linked to said ECM, wherein said supplemental fibronectin attracts, links to and interacts with endogenous stem cells, fibroblasts and endothelial cells in vivo to control and enhance matrix formation and remodeling when said composition is administered to damaged cardiovascular tissue. 
 
     
     
         4 . The composition of  claim 3 , wherein said ECM further comprises an exogenously added cytokine. 
     
     
         5 . An injectable graft composition for myocardial tissue regeneration, said composition comprising acellular extracellular matrix (ECM) from a mammalian tissue source comprising liver basement membrane (LBM), said ECM comprising endogenous matrix metalloproteases (MMPs), transforming growth factor-beta (TGF-β), fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor (VEGF), said ECM further comprising an exogenously added supplemental bioactive component comprising fibronectin, said supplemental fibronectin comprising at least 0.1% by weight of said composition,
 said supplemental fibronectin being linked to said ECM, wherein said supplemental fibronectin attracts, links to and interacts with endogenous stem cells, fibroblasts and endothelial cells in vivo to control and enhance matrix formation and remodeling when said composition is administered to damaged cardiovascular tissue. 
 
     
     
         6 . The composition of  claim 5 , wherein said ECM further comprises an exogenously added cytokine. 
     
     
         7 . An injectable graft composition for myocardial tissue regeneration, said composition comprising acellular extracellular matrix (ECM) from a mammalian tissue source comprising urinary bladder submucosa (UBS), said ECM comprising endogenous matrix metalloproteases (MMPs), transforming growth factor-beta (TGF-β), fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor (VEGF), said ECM further comprising an exogenously added supplemental bioactive component comprising fibronectin, said supplemental fibronectin comprising at least 0.1% by weight of said composition,
 said supplemental fibronectin being linked to said ECM, wherein said supplemental fibronectin attracts, links to and interacts with endogenous stem cells, fibroblasts and endothelial cells in vivo to control and enhance matrix formation and remodeling when said composition is administered to damaged cardiovascular tissue. 
 
     
     
         8 . The composition of  claim 7 , wherein said ECM further comprises an exogenously added cytokine. 
     
     
         9 . An injectable graft composition for myocardial tissue regeneration, said composition comprising acellular extracellular matrix (ECM) from a mammalian tissue source comprising stomach submucosa (SS), said ECM comprising endogenous matrix metalloproteases (MMPs), transforming growth factor-beta (TGF-β), fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor (VEGF), said ECM further comprising an exogenously added supplemental bioactive component comprising fibronectin, said supplemental fibronectin comprising at least 0.1% by weight of said composition,
 said supplemental fibronectin being linked to said ECM, wherein said supplemental fibronectin attracts, links to and interacts with endogenous stem cells, fibroblasts and endothelial cells in vivo to control and enhance matrix formation and remodeling when said composition is administered to damaged cardiovascular tissue. 
 
     
     
         10 . The composition of  claim 9 , wherein said ECM further comprises an exogenously added cytokine. 
     
     
         11 . An injectable graft composition for myocardial tissue regeneration, said composition comprising acellular extracellular matrix (ECM) from a mammalian tissue source comprising placental extracellular matrix, said ECM comprising endogenous matrix metalloproteases (MMPs), transforming growth factor-beta (TGF-β), fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor (VEGF), said ECM further comprising an exogenously added supplemental bioactive component comprising fibronectin, said supplemental fibronectin comprising at least 0.1% by weight of said composition,
 said supplemental fibronectin being linked to said ECM, wherein said supplemental fibronectin attracts, links to and interacts with endogenous stem cells, fibroblasts and endothelial cells in vivo to control and enhance matrix formation and remodeling when said composition is administered to damaged cardiovascular tissue. 
 
     
     
         12 . The composition of  claim 11 , wherein said ECM further comprises an exogenously added cytokine. 
     
     
         13 . An injectable graft composition for myocardial tissue regeneration, said composition comprising acellular extracellular matrix (ECM) from a mammalian tissue source comprising heart extracellular matrix, said ECM comprising endogenous matrix metalloproteases (MMPs), transforming growth factor-beta (TGF-β), fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor (VEGF), said ECM further comprising an exogenously added supplemental bioactive component comprising fibronectin, said supplemental fibronectin comprising at least 0.1% by weight of said composition,
 said supplemental fibronectin being linked to said ECM, wherein said supplemental fibronectin attracts, links to and interacts with endogenous stem cells, fibroblasts and endothelial cells in vivo to control and enhance matrix formation and remodeling when said composition is administered to damaged cardiovascular tissue. 
 
     
     
         14 . The composition of  claim 13 , wherein said ECM further comprises an exogenously added cytokine.