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 can also have an extracellular matrix scaffold component of any formulation, then including also added cells, proteins, or other components to optimize the regenerative process and restore cardiac function. Methods for regenerating defective or absent myocardium apply a composition to a site of myocardium in need of regeneration using a delivery mode appropriate for the particular formulation.

1 . A composition comprising at least a portion of an extracellular matrix scaffold component derived from a mammalian or synthetic source and a first additional component selected from the group consisting of a collagen present in myocardial tissue, a collagen type IV protein, a collagen type VIII protein, a collagen type X protein, a multiplexin, a matrix heparin sulfate protoeglycan, a laminin, a nidogen, an agin, and a perlecan, and also comprising a second additional component selected from the groups consisting of: 
 a) a plurality of synthetic extracellular matrix-like scaffold-forming molecules    b) a cell,    c) a peptide, polypeptide, or protein, and    d) a vector having a DNA capable of targeted expression of a selected gene, and    e) a nutrient, a sugar, a fat, a lipid, an amino acid, a nucleic acid, a ribo-nucleic acid, an organic molecule, an inorganic molecule, a small molecule, a drug, or a bioactive molecule.    
     
     
         2 . The composition of  claim 1 , wherein said scaffold is formulated in a material form selected from the group consisting of a solid sheet, multilaminate sheets, a gel, an emulsion, an injectable solution, a fluid, a paste, a powder, a plug, a strand, a suture, a coil, a cylinder, a weave, a strip, a spray, a vapor, a patch, a sponge, a cream, a coating, a lyophilized material, and a vacuum-pressed material.  
     
     
         3 . The composition of  claim 1  or  2 , wherein said first or second additional component is formulated in a material form selected from the group consisting of a gel, an emulsion, an injectable solution, a fluid, a paste, a powder, a plug, a strand, a spray, a vapor, a cream, a coating, a lyophilized material and a vacuum-pressed material.  
     
     
         4 . The composition of  claim 1 , wherein the extracellular matrix scaffold component is derived from a source selected from the group consisting of small intestine submucosa (SIS), urinary bladder submucosa (UBS), urinary basement membrane (UBM), liver basement membrane (LBM), stomach submucosa (SS), collagen from animal sources, collagen from plant sources, synthesized extracellular matrix in cultures from cells (Matrigel™), dermal extracellular matrix material, subcutaneous extracellular matrix material, large intestine extracellular matrix material, placental extracellular matrix material, ornamentum extracellular matrix material, heart extracellular matrix material, and lung extracellular matrix material.  
     
     
         5 . The composition of  claim 1 , wherein the second additional component is a plurality of synthetic extracellular matrix-like scaffold-forming molecules, and said synthetic molecules are selected from the group consisting of polyethylene terephthalate fiber (Dacron), polytetrafluoroethylene (PTFE), glutaraldehyde-cross linked pericardium, polylactate (PLA), polyglycol (PGA), hyaluronic acid, polyethylene glycol (PEG), polyethelene, a nucleic acid polymer, nitinol, and collagen from non-animal sources.  
     
     
         6 . The composition of  claim 1 , wherein the second additional component is a cell, and the cell is selected from the group consisting of a human embryonic stem cell, a fetal cardiomyocyte, a myofibroblast, a mesenchymal stem cell, an autotransplanted expanded cardiomyocyte, an adipocyte, a totipotent cell, a pluripotent cell, a blood stem cell, a myoblast, an adult stem cell, a bone marrow cell, a mesenchymal cell, an embryonic stem cell, a parenchymal cell, an epithelial cell, an endothelial cell, a mesothelial cell, a fibroblast, a myofibroblast, an osteoblast, a chondrocyte, an exogenous cell, an endogenous cell, a stem cell, a hematopoetic stem cell, a pluripotent stem cell, a bone marrow-derived progenitor cell, a progenitor cell, a myocardial cell, a skeletal cell, a fetal cell, an embryonic cell, an undifferentiated cell, a multi-potent progenitor cell, a unipotent progenitor cell, a monocyte, a cardiomyocyte, a cardiac myoblast, a skeletal myoblast, a macrophage, a capillary endothelial cel, a xenogenic cell, an allogenic cell, an adult stem cell, and a post-natal stem cell.  
     
     
         7 . The composition of  claim 1 , wherein the second additional component is a peptide, polypeptide, or protein, and said peptide, polypeptide, or protein selected from the group consisting of a collagen, a proteoglycan, a glycosaminoglycan (GAG) chain, a glycoprotein, a growth factor, a cytokine, a cell-surface associated protein, a cell adhesion molecule (CAM), an angiogenic growth factor, an endothelial ligand, a matrikine, a matrix metalloprotease, a cadherin, an immunoglobin, a fibril collagen, a non-fibrillar collagen, a basement membrane collagen, a multiplexin, a small-leucine rich proteoglycan, decorin, biglycan, a fibromodulin, keratocan, lumican, epiphycan, a heparan sulfate proteoglycan, perlecan, agrin, testican, syndecan, glypican, serglycin, selectin, a lectican, aggrecan, versican, nuerocan, brevican, cytoplasmic domain-44 (CD-44), macrophage stimulating factor, amyloid precursor protein, heparin, chondroitin sulfate B (dermatan sulfate), chondroitin sulfate A, heparan sulfate, hyaluronic acid, fibronectin (Fn), tenascin, elastin, fibrillin, laminin, nidogen/entactin, fibulin I, fibulin II, integrin, a transmembrane molecule, platelet derived growth factor (PDGF), epidermal growth factor (EGF), transforming growth factor alpha (TGF-alpha), transforming growth factor beta (TGF-beta), fibroblast growth factor-2 (FGF-2) (also called basic fibroblast growth factor (bFGF)), thrombospondin, osteopontin, angiotensin converting enzyme (ACE), and vascular epithelial growth factor (VEGF).