Methods for using a three-dimensional stromal tissue to promote angiogenesis

Abstract

The present invention relates to a method for promoting blood vessel formation in tissues and organs. In particular, the method relates to implantation or attachment of an engineered three-dimensional stromal tissue to promote endothelialization and angiogenesis in the heart and related tissues. The three-dimensional stromal tissue of the present invention may be used in a variety of applications including, but not limited to, promoting repair of and regeneration of damaged cardiac muscle, promoting vascularization and healing during cardiac surgery, promoting blood vessel formation at anastomosis sites, and promoting vascularization and repair of damaged skeletal muscle, smooth muscle or connective tissue.

What is claimed is:  
     
         1 . A method for promoting angiogenesis in the heart of a subject, comprising attaching a three-dimensional stromal tissue to the heart of the subject to increase the number of blood vessels in the heart, said stromal tissue comprises stromal cells and connective tissue proteins naturally secreted by the stromal cells attached to and substantially enveloping a framework composed of a biocompatible, non-living material formed into a three-dimensional structure having interstitial spaces bridged by the stromal cells.  
     
     
         2 . The method of  claim 1  wherein the three-dimensional stromal tissue is living.  
     
     
         3 . The method of  claim 1  wherein the stromal cells are fibroblasts, smooth muscle cells, cardiac muscle cells, endothelial cells, pericytes, macrophages, monocytes, leukocytes, plasma cells, mast cells, adiposites, or any combination thereof.  
     
     
         4 . The method of  claim 3  wherein the smooth muscle cells are aortic smooth muscle cells.  
     
     
         5 . The method of  claim 1  wherein the framework is composed of a biodegradable material.  
     
     
         6 . The method of  claim 5  wherein the biodegradable material is cotton, polyglycolic acid, cat gut sutures, cellulose, gelatin, collagen gel or dextran.  
     
     
         7 . The method of  claim 1  wherein the framework is composed of a non-biodegradable material.  
     
     
         8 . The method of  claim 7  wherein the non-biodegradable material is a polyamide, a polyester, a polystyrene, a polypropylene, a polyacrylate, a polyvinyl, a polycarbonate, a polytetrafluorethylene or a nitrocellulose compound.  
     
     
         9 . The method of  claim 1  wherein the framework is a mesh.  
     
     
         10 . The method of  claim 1  wherein the stromal tissue is obtained directly from a fresh culture.  
     
     
         11 . The method of  claim 1  wherein the stromal tissue has been cryopreserved.  
     
     
         12 . The method of  claim 1  wherein the stromal tissue is adhered to the heart by natural cellular attachment.  
     
     
         13 . The method of  claim 1  wherein the stromal tissue is attached to the heart by an attachment means.  
     
     
         14 . The method of  claim 13  wherein the attachment means is a suture, a biologic glue, a synthetic glue, a laser dye or a hydrogel.  
     
     
         15 . The method of  claim 14  wherein the biologic glue is a fibrin glue.  
     
     
         16 . The method of  claim 1 , wherein the stromal tissue is attached to the heart epicardium.  
     
     
         17 . The method of  claim 1  wherein the stromal tissue is attached to the heart myocardium.  
     
     
         18 . The method of  claim 1  in which the stromal tissue is attached to the heart endocardium.  
     
     
         19 . A method for promoting vascularization of a mammalian tissue in vivo, comprising attaching a three-dimensional stromal tissue to the mammalian tissue to increase the number of blood vessels in the mammalian tissue, said stromal tissue comprising stromal cells attached to and substantially enveloping a framework composed of a biocompatible, non-living material formed into a three-dimensional structure having interstitial spaces bridged by the stromal cells.  
     
     
         20 . The method of  claim 19 , wherein the mammalian tissue is cardiac tissue, skeletal muscle, smooth muscle, connective tissue or skin tissue.  
     
     
         21 . The method of  claim 19  wherein the stromal cells are fibroblasts, smooth muscle cells, cardiac muscle cells, endothelial cells, pericytes, macrophages, monocytes, leukocytes, plasma cells, mast cells, adiposites, or any combination thereof.  
     
     
         22 . The method of  claim 19  wherein the framework is composed of a biodegradable material.  
     
     
         23 . The method of  claim 22  wherein the biodegradable material is cotton, polyglycolic acid, cat gut sutures, cellulose, gelatin, collagen gel or dextran.  
     
     
         24 . The method of  claim 19  wherein the framework is composed of a non-biodegradable material.  
     
     
         25 . The method of  claim 24  wherein the non-biodegradable material is a polyamide, a polyester, a polystyrene, a polypropylene, a polyacrylate, a polyvinyl, a polycarbonate, a polytetrafluorethylene or a nitrocellulose compound.  
     
     
         26 . The method of  claim 19  wherein the framework is a mesh.  
     
     
         27 . The method of  claim 19  wherein the stromal tissue is obtained directly from a fresh culture.  
     
     
         28 . The method of  claim 19  wherein the stromal tissue has been cryopreserved.  
     
     
         29 . The method of  claim 19  wherein the stromal tissue is adhered to the mammalian tissue by natural cellular attachment.  
     
     
         30 . The method of  claim 29  wherein the stromal tissue is attached to the mammalian tissue by an attachment means.  
     
     
         31 . The method of  claim 30  wherein the attachment means is a suture, a biologic glue, a synthetic glue, a laser dye or a hydrogel.  
     
     
         32 . A method for promoting healing of a site of anastomosis in a subject, comprising attaching a three-dimensional stromal tissue to the site to promote growth of endothelial cells and increase the number of blood vessels in the site, wherein said stromal tissue comprises stromal cells and connective tissue proteins naturally secreted by the stromal cells attached to and substantially enveloping a framework composed of a biocompatible, non-living material formed into a three-dimensional structure having interstitial spaces bridged by the stromal cells.  
     
     
         33 . The method of  claim 32 , wherein the step of attaching comprises wrapping a three-dimensional stromal tissue around the site of anastomosis to promote endothelialization of the site.  
     
     
         34 . The method of  claim 32 , wherein the stromal cells are fibroblasts, smooth muscle cells, cardiac muscle cells, endothelial cells, pericytes, macrophages, monocytes, leukocytes, plasma cells, mast cells, adiposites or any combination thereof.  
     
     
         35 . The method of  claim 32  wherein the framework is composed of a biodegradable material.  
     
     
         36 . The method of  claim 35  wherein the biodegradable material is cotton, polyglycolic acid, cat gut sutures, cellulose, gelatin, collagen gel or dextran.  
     
     
         37 . The method of  claim 32  wherein the framework is composed of a non-biodegradable material.  
     
     
         38 . The method of  claim 37  wherein the non-biodegradable material is a polyamide, a polyester, a polystyrene, a polypropylene, a polyacrylate, a polyvinyl, a polycarbonate, a polytetrafluorethylene or a nitrocellulose compound.  
     
     
         39 . The method of  claim 32  wherein the framework is a mesh.  
     
     
         40 . The method of  claim 32  wherein the stromal tissue is adhered to the site by natural cellular attachment.  
     
     
         41 . The method of  claim 32  wherein the stromal tissue is attached to the site by any of a suture, a biologic glue, a synthetic glue, a laser dye, or a hydrogel.