Compositions and methods for tissue repair

Abstract

The present invention provides compositions and methods for targeting an extracellular matrix derived (EMD) peptide predominantly to an injured tissue, as opposed to an uninjured tissue in vivo. The targeted EMD peptide facilitates the repair and/or regeneration of the injured tissue by providing a surface for cells to attach and grow, thereby facilitating the repair and/or regeneration of the injured tissue.

What is claimed is: 
     
         1 . A composition for repair of an injured tissue, the composition comprising an injury-associated antigen-specific binding component conjugated to an extracellular matrix derived (EMD) peptide,
 wherein the injury-associated antigen-specific binding component comprising a molecule that specifically binds an antigen expressed following tissue injury, and   wherein the EMD peptide is a peptide or a concatamer of a peptide that ranges in length from about 8 amino acid residues to about 100 amino acid residues, and exhibits the ability to: (i) activate cells; (ii) attach cells; and (iii) exhibits a chemotropic property.   
     
     
         2 . The composition of  claim 1 , wherein the EMD peptide further exhibits an angiogenic property. 
     
     
         3 . The composition of  claim 1 , wherein the EMD peptide is a concatamer. 
     
     
         4 . The composition of  claim 1 , wherein the EMD peptide is selected from the group consisting of a Hep III peptide as shown in SEQ ID NO:2, and an RGD peptide as shown in SEQ ID NO:4. 
     
     
         5 . The composition of  claim 1 , wherein the EMD peptide is derived from a protein selected from the group consisting of collagen, laminin, tenascin-C, fibronectin, fibrin, and elastin. 
     
     
         6 . The composition of  claim 1 , wherein the injury-associated antigen is a member selected from the group consisting of: myosin light chain, myosin heavy chain, troponin I, VCAM-1, ICAM-1, P-selectin, E-selectin, L-selectin, Mo1/CD18, TNF receptor-1, TNF receptor-2, caspase-3, VAP-1, annexin, osteopontin, thrombospondin, laminin, fibronectin, and collagen. 
     
     
         7 . The composition of  claim 1 , wherein the injury-associated antigen-specific binding component and the EMD peptide is chemically or recombinantly conjugated. 
     
     
         8 . The composition of  claim 1 , wherein the injury-associated antigen-specific binding component is an antibody. 
     
     
         9 . The composition of  claim 8 , wherein the antibody is selected from the group consisting of: a (Fab)′2 fragment, an ScFv, a human antibody, and a humanized antibody. 
     
     
         10 . The composition of  claim 1 , wherein the injury-associated antigen-specific binding component is an antibody mimetic. 
     
     
         11 . The composition of  claim 1 , wherein the tissue is selected from the group consisting of: cardiac, cartilage, bone, bone marrow, dental, hepatic, neural, vascular, and renal. 
     
     
         12 . The composition of  claim 1 , further comprising a pharmaceutically acceptable excipient. 
     
     
         13 . A method for repairing an injured tissue, the method comprising administering to a mammalian subject a composition having an injury-associated antigen-specific binding component conjugated to an extracellular matrix derived (EMD) peptide,
 wherein the injury-associated antigen-specific binding component comprising a molecule that specifically binds an antigen expressed following tissue injury, and   wherein the EMD peptide is a peptide or a concatamer of a peptide that ranges in length from about 8 amino acid residues to about 100 amino acid residues, and exhibits the ability to: (i) activate cells; (ii) attach cells; and (iii) exhibits a chemotropic property and   wherein said composition is administered in an amount sufficient to facilitate repair or regeneration of the injured tissue.   
     
     
         14 . The method of  claim 13 , wherein the EMD peptide further exhibits an angiogenic property. 
     
     
         15 . The method of  claim 13 , wherein the EMD peptide is a concatamer. 
     
     
         16 . The method of  claim 13 , wherein the EMD peptide is selected from the group consisting of a Hep III peptide as shown in SEQ ID NO:2 and an RGD peptide as shown in SEQ ID NO:4. 
     
     
         17 . The method of  claim 13 , wherein the EMD peptide is derived from a protein selected from the group consisting of collagen, laminin, tenascin-C, fibronectin, fibrin, and elastin. 
     
     
         18 . The method of  claim 13 , wherein the injury-associated antigen is a member selected from the group consisting of: myosin light chain, myosin heavy chain, troponin I, caspase-3, VCAM-1, ICAM-1, P-selectin, E-selectin, L-selectin, Mo1/CD18, TNF receptor-1, TNF receptor-2, VAP-1, annexin, osteopontin, thrombospondin, laminin, fibronectin, and collagen. 
     
     
         19 . The method of  claim 13 , wherein the injury-associated antigen-specific binding component is an antibody. 
     
     
         20 . The method of  claim 19 , wherein the antibody is selected form the group consisting of: a (Fab)′2 fragment, an ScFv, a human antibody, and a humanized antibody. 
     
     
         21 . The method of  claim 13 , wherein the injury-associated antigen-specific binding component is an antibody mimetic. 
     
     
         22 . The method of  claim 13 , wherein the injury-associated antigen-specific binding component and the EMD peptide is chemically or recombinantly conjugated. 
     
     
         23 . The method of  claim 13 , wherein the tissue is selected from the group consisting of: cardiac, cartilage, bone, bone marrow, dental, neural, vascular, hepatic and renal. 
     
     
         24 . The method of  claim 13 , wherein the mammalian subject is a human. 
     
     
         25 . The method of  claim 24 , wherein the human has been diagnosed with ischemic cardiovascular disease. 
     
     
         26 . The method of  claim 25 , wherein the ischemic cardiovascular disease is selected from the group consisting of: myocardial infarction, peripheral vascular disease, stroke, myocardial conduction disorder, and congestive heart failure.