Compositions and Structures for Regenerating Defective or Absent Myocardium

Abstract

Sheet structures for regenerating damaged or diseased mammalian tissue that are formed from acellular dermal mammalian tissue. The acellular dermal mammalian tissue includes extracellular matrix (ECM) and a supplemental bioactive component. The supplemental bioactive component can comprise a nucleic acid, such as RNA, and/or a cell, such as an embryonic stem cell. The sheet structures induce angiogenesis and, thereby, regeneration of new mammalian tissue.

What is claimed is: 
     
         1 . A sheet structure for regenerating damaged or diseased mammalian tissue, comprising:
 acellular dermal mammalian tissue, said acellular dermal mammalian tissue comprising extracellular matrix (ECM),   said ECM comprising collagen type I, collagen type III, proteoglycans, transforming growth factor beta (TGF-β) and fibroblast growth factor-2 (FGF-2),   said acellular dermal mammalian tissue further comprising a supplemental bioactive component comprising an exogenously added cell selected from the group consisting of an embryonic stem cell, a mesenchymal cell and a hematopoietic stem cell,   said exogenously added cell being linked to said ECM, wherein said exogenously added cell interacts with at least one molecule in said ECM, whereby, when said acellular dermal mammalian tissue is disposed proximate to damaged mammalian tissue, said acellular dermal mammalian tissue induces angiogenesis and, thereby, regeneration of new mammalian tissue.   
     
     
         2 . The sheet structure of  claim 1 , wherein said damaged mammalian tissue comprises damaged cardiovascular tissue. 
     
     
         3 . The sheet structure of  claim 2 , wherein said exogenously added cell is selected from the group consisting of a neonatal cardiomyocyte, a fetal cardiomyocyte and a myofibroblast. 
     
     
         4 . The sheet structure of  claim 1 , wherein said acellular dermal mammalian tissue comprises a physical formulation selected from the group consisting of a solid sheet, a multilaminate sheet, a weave, a strip, a patch and a vacuum pressed material. 
     
     
         5 . A sheet structure for regenerating damaged or diseased mammalian tissue, comprising:
 acellular dermal mammalian tissue, said acellular dermal mammalian tissue comprising extracellular matrix (ECM),   said ECM comprising collagen type I, collagen type III, proteoglycans, transforming growth factor beta (TGF-β) and fibroblast growth factor-2 (FGF-2),   said acellular dermal mammalian tissue further comprising a supplemental bioactive component comprising an exogenously added nucleic acid, said exogenously added nucleic acid being linked to said ECM, wherein said exogenously added nucleic acid interacts with said ECM, whereby, when said acellular dermal mammalian tissue is disposed proximate to damaged mammalian tissue, said acellular dermal mammalian tissue modulates matrix formation and induces angiogenesis and, thereby, regeneration of new mammalian tissue.   
     
     
         6 . The sheet structure of  claim 5 , wherein said damaged mammalian tissue comprises damaged cardiovascular tissue. 
     
     
         7 . The sheet structure of  claim 6 , wherein said acellular dermal mammalian tissue further comprises an exogenously added cell. 
     
     
         8 . The sheet structure of  claim 7 , wherein said exogenously added cell is selected from the group consisting of an embryonic stem cell, a mesenchymal cell, a hematopoietic stem cell, a neonatal cardiomyocyte, a fetal cardiomyocyte and a myofibroblast. 
     
     
         9 . The sheet structure of  claim 5 , wherein said acellular dermal mammalian tissue comprises a physical formulation selected from the group consisting of a solid sheet, a multilaminate sheet, a weave, a strip, a patch and a vacuum pressed material. 
     
     
         10 . The sheet structure of  claim 5 , wherein said exogenously added nucleic acid comprises DNA. 
     
     
         11 . The sheet structure of  claim 5 , wherein said exogenously added nucleic acid comprises cDNA. 
     
     
         12 . The sheet structure of  claim 5 , wherein said exogenously added nucleic acid comprises RNA. 
     
     
         13 . The sheet structure of  claim 12 , wherein said RNA comprises mRNA. 
     
     
         14 . The sheet structure of  claim 12 , wherein said RNA comprises tRNA. 
     
     
         15 . The sheet structure of  claim 12 , wherein said RNA comprises rRNA. 
     
     
         12 . The sheet structure of  claim 12 , wherein said RNA comprises synthetic RNA.