Cardiac valve replacement

Abstract

The invention provides a replacement heart valve which contains an acellular matrix as a structural scaffold. The scaffold is seeded with isolated myofibroblasts and/or endothelial cells prior to implantation into a recipient mammal.

What is claimed is:  
     
         1 . A bioprosthetic heart valve comprising an acellular matrix and isolated myofibroblasts wherein at least 60% of the total collagen produced by said myofibroblasts is type I collagen.  
     
     
         2 . The valve of  claim 1 , wherein said myofibroblasts produce at least 2-fold greater type I collagen compared to type III collagen.  
     
     
         3 . The valve of  claim 1 , wherein said myofibroblasts produce one or more extracellular matrix components selected from the group consisting of fibronectin, elastin, and glycosaminoglycan.  
     
     
         4 . The valve of  claim 3 , wherein said glycosaminoglycan is chondroitin sulfate or hyaluronic acid.  
     
     
         5 . A valve comprising an acellular matrix and an isolated myofibroblast, wherein less than 25% of total collagen production by said myofibroblast is type III collagen.  
     
     
         6 . The valve of  claim 5 , wherein less than 20% of total collagen production by said myofibroblast is type III collagen.  
     
     
         7 . The valve of  claim 5 , wherein less than 15% of total collagen production by said myofibroblast is type m collagen.  
     
     
         8 . The valve of  claim 5 , wherein said myofibroblast is derived from mammalian heart leaflet interstitial tissue.  
     
     
         9 . The valve of  claim 5 , wherein said myofibroblast is derived from a mammalian vascular or dermal tissue.  
     
     
         10 . The valve of  claim 5 , wherein said myofibroblast is derived from human heart leaflet interstitial tissue.  
     
     
         11 . A method of enhancing production of type I collagen by an isolated myofibroblast, comprising culturing said myofibroblast under pulsatile flow conditions.  
     
     
         12 . The method of  claim 11 , wherein said myofibroblast is cultured in the presence of basic fibroblast growth factor.  
     
     
         13 . The method of  claim 11 , wherein said myofibroblast is cultured in endothelial cell-conditioned media.  
     
     
         14 . The method of  claim 11 , wherein said myofibrobast is cultured in the presence of an isolated endothelial cell.  
     
     
         15 . A method of enhancing viability and contractile activity of myofibroblasts in vitro comprising culturing said myofibroblast under pulsatile flow conditions.  
     
     
         16 . The method of  claim 15 , wherein said myofibroblast is cultured in endothelial cell-conditioned media.  
     
     
         17 . The method of  claim 15 , wherein said myofibrobast is cultured in the presence of an isolated endothelial cell.  
     
     
         18 . The method of  claim 15 , wherein said myofibroblast is cultured in the presence of a purified endothelial cell-derived growth factor, wherein said growth factor inhibits apoptosis of said myofibroblast.  
     
     
         19 . An isolated myofibroblast, wherein said myofibroblast is genetically altered to increase type I collagen production relative to type III collagen production.  
     
     
         20 . A bioprosthetic heart valve comprising the myofibroblast of  claim 19 .  
     
     
         21 . A method of manufacturing an artificial heart valve, comprising 
 (a) providing an acellular matrix,    (b) seeding said matrix with isolated myofibroblasts; and    (c) culturing said myofibroblasts under pulsatile flow conditions.    
     
     
         22 . The method of  claim 21 , wherein said myofibroblasts are derived from an intended recipient from an intended recipient of said centrifugal heart valve.