Therapeutic compositions and methods for enhancing angiogenesis

Abstract

The present inventors have surprisingly found that the Mts-1 protein stimulates angiogenesis. In particular, the present inventors have found that Mts-1 transgenic mice developed hemangiomas and stenosis. The present inventors have also found that addition of Mts-1 proteins to the culture media increases the motility of mouse endothelial cells. Further, the present inventors have found that injection of Mts1 proteins stimulates angiogenesis in the mouse corneas. Accordingly, the present invention provides methods of enhancing angiogenesis in a subject in need thereof by administering a therapeutically effective amount of an angiogenic Mts-1 component.

We claim:  
     
         1 . A method of enhancing angiogenesis in a tissue or organ of a subject in need thereof, which comprises administering a therapeutically effective amount of an angiogenic Mts-1 component to the subject.  
     
     
         2 . The method of  claim 1 , wherein said tissue or organ is a damaged tissue or organ, or a transplant tissue or organ.  
     
     
         3 . The method of  claim 2 , wherein said tissue is cardiac tissue, brain tissue, skin, tissue of gastrointestinal tract, or tissue of urinal tract.  
     
     
         4 . The method of  claim 2 , wherein said organ is heart.  
     
     
         5 . The method of  claim 1 , wherein said Mts-1 component is a Mts-1 protein or a functional fragment or analog thereof.  
     
     
         6 . The method of  claim 1 , wherein said Mts-1 component is a nucleic acid molecule encoding a Mts-l protein or a functional fragment or analog thereof.  
     
     
         7 . The method of  claim 6 , wherein said nucleic acid molecule is placed in an expression vector selected from a plasmid, retroviral, polio viral, adenoviral, adeno-associated viral, herpes viral, SV 40, or vaccinia vector.  
     
     
         8 . The method of  claim 1 , wherein said carrier is oil, water, saline solution, gel, lipid, liposome, or a porous matrix material.  
     
     
         9 . The method of  claim 1 , wherein said carrier is capable of a controlled release of said Mts-1 component.  
     
     
         10 . The method of  claim 1 , wherein said Mts-1 component in a pharmaceutically acceptable carrier is administered to the subject via an oral, ophthalmic, nasal, topical, transdermal, parenteral, intracranial, intracerebral, intraspinal, intravaginal, intrauterine, or rectal route.  
     
     
         11 . The method of  claim 1 , wherein said Mts-1 component in a pharmaceutically acceptable carrier is administered to the subject by injection or surgical implantation proximate to a preselected tissue or organ site in need of angiogenesis.  
     
     
         12 . An angiogenic composition, comprising an Mts-1 component and a pharmaceutically acceptable carrier.  
     
     
         13 . The angiogenic composition of  claim 12 , wherein said Mts-1 component is a Mts-1 protein or a functional fragment or analog thereof.  
     
     
         14 . The angiogenic composition of  claim 12 , wherein said Mts-1 component is a nucleic acid molecule encoding an Mts-1 protein or a functional fragment or analog thereof.  
     
     
         15 . The angiogenic composition of  claim 12 , wherein said nucleic acid molecule is provided in an expression vector selected from a plasmid, retroviral, polio viral, adenoviral, adeno-associated viral, herpes viral, SV 40, or vaccinia vector.