Compositions and Methods for Tissue Repair with Extracellular Matrices

Abstract

Described herein are compositions comprising decellularized cardiac extracellular matrix and therapeutic uses thereof. Methods for treating, repairing or regenerating defective, diseased, damaged or ischemic cells, tissues or organs in a subject, preferably a human, using a decellularized cardiac extracellular matrix of the invention are provided. Methods of preparing cardiomyocyte culture surfaces and culturing cells with absorbed decellularized cardiac extracellular matrix are provided.

1 . A composition comprising decellularized extracellular matrix derived from cardiac or skeletal muscle tissue, wherein said decellularized extracellular matrix retains native tissue specific proteins and glycosaminoglycans, and wherein said composition is in a solution form at a temperature between 20° C.-25° C. and in a gel form at a temperature greater than 25° C. 
     
     
         2 . The composition of  claim 1 , wherein said composition comprises naturally or non-naturally occurring factors that recruit cells into the composition. 
     
     
         3 . The composition of  claim 1 , wherein said composition is injectable and is formulated to be delivered through a 27G or smaller needle for tissue repair or regeneration. 
     
     
         4 . The composition of  claim 1 , wherein said composition further comprises cells selected from the group consisting of pluripotent stem cells, multipotent stem cells, cardiomyocytes, cardiac progenitor cells, skeletal myoblasts, or skeletal muscle progenitor cells. 
     
     
         5 . The composition of  claim 1 , wherein said composition further comprises an exogenous therapeutic agent or a polymer in a therapeutically acceptable formulation. 
     
     
         6 . The composition of  claim 1 , wherein said composition further comprises cells, drugs, proteins, or polysaccharides that can be delivered inside, attached to the composition before, during, or after gelation. 
     
     
         7 . The composition of  claim 1 , wherein said composition comprising the decellularized extracellular matrix from cardiac tissue is formulated to coat tissue culture plates to culture cardiomyocytes or other cardiac cell progenitors. 
     
     
         8 . The composition of  claim 1 , wherein the composition comprising the decellularized extracellular matrix from cardiac tissue is formulated to be injected or implanted into the infarct wall following a myocardial infarction for cardiac tissue repair or regeneration. 
     
     
         9 . The composition of  claim 1 , wherein said composition comprising the decellularized extracellular matrix from skeletal muscle tissue is formulated to coat tissue culture plates to culture skeletal myoblasts or other skeletal muscle progenitor cells. 
     
     
         10 . The composition of  claim 1 , wherein the composition comprising the decellularized extracellular matrix from skeletal muscle tissue is formulated to be injected or implanted in a body for skeletal muscle repair or regeneration. 
     
     
         11 . A method of producing a composition comprising decellularized extracellular matrix from cardiac or skeletal muscle tissue, comprising:
 (a) obtaining a cardiac or skeletal muscle tissue sample having an extracellular matrix component and a non-extracellular matrix component;   (b) processing the cardiac or skeletal muscle tissue sample with a detergent to remove the non-extracellular matrix component to obtain decellularized cardiac extracellular matrix; and   (c) sterilizing the decellularized cardiac or skeletal muscle extracellular matrix.   
     
     
         12 . The method of  claim 11 , further comprising a step of lyophilizing and grinding up the decellularized cardiac or skeletal muscle extracellular matrix. 
     
     
         13 . The method of  claim 11 , further comprising a step of enzymatically treating the decellularized cardiac or skeletal muscle extracellular matrix. 
     
     
         14 . The method of  claim 11 , further comprising a step of suspending and neutralizing said decellularized cardiac or skeletal muscle extracellular matrix in a saline buffered solution. 
     
     
         15 . The method of  claim 14 , wherein said resulting saline buffered solution comprising said decellularized cardiac or skeletal muscle extracellular matrix is injectable through a 27G or smaller needle at 20° C.-25° C., and spontaneously forms in a gel form at a temperature greater than 25° C. 
     
     
         16 . The method of  claim 14 , wherein said resulting saline buffered solution comprising said decellularized cardiac or skeletal muscle extracellular matrix further comprises cells, drugs, proteins, or polysaccharides that can be delivered inside, attached to the solution before, during, or after gelation. 
     
     
         17 . The method of  claim 14 , further comprising placing said resulting saline buffered solution comprising said decellularized cardiac or skeletal muscle extracellular matrix into tissue culture plates or wells to form into an adsorbed matrix for culturing cells. 
     
     
         18 . A method of culturing cells on an adsorbed matrix comprising the steps of:
 (a) providing a solution comprising decellularized extracellular matrix derived from cardiac or skeletal muscle tissue into a tissue culture device;   (b) incubating said tissue culture device to absorb at least some of the decellularized extracellular matrix onto the device;   (c) removing said solution; and   (d) culturing cells on the adsorbed matrix.   
     
     
         19 . The method of  claim 18 , wherein said cells are cardiomyocytes, cardiac cell progenitors, or other cell types relevant to cardiac tissue repair. 
     
     
         20 . The method of  claim 18 , wherein said cells are skeletal myoblasts, skeletal muscle progenitor cells, or other cell types relevant to skeletal muscle tissue repair.