Prosthetic Grafts

Abstract

An improved prosthetic graft for the bypass, replacement or repair of vessels and organs that are in contact with blood flow is disclosed. The prosthetic graft includes a porous prosthetic implant and adherent cells adhered to the outer surface of the implant. The adherent cells are transfected with at least one recombinant nucleic acid molecule encoding at least one protein that enhances patency of the graft. The prosthetic graft has a long-term patency and success rate that is superior to other previously described prosthetic grafts designed for such use. Also disclosed are methods of making and using such a graft.

1 .- 103 . (canceled)  
     
     
         104 . A method of implanting a prosthetic graft for containment of blood flow into a patient, comprising: 
 implanting into the patient a prosthetic graft comprising (a) a porous prosthetic implant for containing blood in vivo, said prosthetic implant having an outer surface that is not in contact with blood flow in vivo and an inner surface that is in contact with blood flow in vivo, said inner surface defining an interior space for containment of blood flow, and (b) adherent cells adhered to the outer surface of said porous prosthetic implant, wherein said adherent cells are not seeded on the inner surface of said porous prosthetic implant, wherein said adherent cells are transfected with at least one recombinant nucleic acid molecule operatively linked to a transcription control sequence, said recombinant nucleic acid molecule encoding a protein that enhances patency of the prosthetic implant.    
     
     
         105 . The method of  claim 104 , further comprising, before the implanting step, harvesting fibroblast cells from said patient.  
     
     
         106 . The method of  claim 105 , further comprising transfecting said fibroblast cells with an isolated nucleic acid molecule encoding a protein that enhances patency of the graft.  
     
     
         107 . The method of  claim 106 , further comprising applying the transfected fibroblast cells to the outer surface of said prosthetic implant.  
     
     
         108 . The method of  claim 104 , wherein said adherent cells are undifferentiated stem cells.  
     
     
         109 . The method of  claim 104 , wherein said adherent cells are embryonal cells.  
     
     
         110 . The method of  claim 104 , wherein said protein is selected from the group consisting of a protein that inhibits angiogenesis, a protein that inhibits thrombosis, a protein that causes thrombolysis, a protein that inhibits smooth muscle migration or proliferation, and a vasodilator protein.  
     
     
         111 . The method of  claim 104 , wherein the transcription control sequence is an inducible promoter, and further comprising administering to the patient a compound which induces the promoter.  
     
     
         112 . The method of  claim 111 , wherein administering is performed via a route selected from the group consisting of oral, nasal, topical, transdermal, rectal, subcutaneous, intradermal, intravenous, and intramuscular.  
     
     
         113 . A method of implanting a prosthetic graft for containment of blood flow into a patient, comprising: 
 implanting into the patient a prosthetic graft comprising (a) a porous prosthetic implant for containing blood in vivo, said prosthetic implant having an outer surface that is not in contact with blood flow in vivo and an inner surface that is in contact with blood flow in vivo, said inner surface defining an interior space for containment of blood flow, and (b) naturally adherent cells adhered to the outer surface of said porous prosthetic implant, wherein said naturally adherent cells are not seeded on the inner surface of said porous prosthetic implant, wherein said naturally adherent cells are transfected with at least one recombinant nucleic acid molecule operatively linked to a transcription control sequence, said recombinant nucleic acid molecule encoding a protein, wherein said protein is expressed by said cells ex vivo, wherein at least a portion of said protein, upon secretion from said cells, perfuses through pores of said prosthetic implant to said inner surface of said prosthetic implant, and wherein said protein is selected from the group consisting of a protein that inhibits angiogenesis, a protein that inhibits thrombosis, a protein that causes thrombolysis, a protein that inhibits smooth muscle migration or proliferation, and a vasodilator protein.    
     
     
         114 . The method of  claim 113 , further comprising, before the implanting step, harvesting fibroblast cells from said patient.  
     
     
         115 . The method of  claim 114 , further comprising transfecting said fibroblast cells with an isolated nucleic acid molecule encoding a protein that enhances patency of the graft.  
     
     
         116 . The method of  claim 115 , further comprising applying the transfected fibroblast cells to the outer surface of said prosthetic implant.  
     
     
         117 . The method of  claim 113 , wherein said adherent cells are undifferentiated stem cells.  
     
     
         118 . The method of  claim 113 , wherein said adherent cells are embryonal cells.  
     
     
         119 . The method of  claim 113 , wherein the transcription control sequence is an inducible promoter, and further comprising administering to the patient a compound which induces the promoter.  
     
     
         120 . The method of  claim 119 , wherein administering is performed via a route selected from the group consisting of oral, nasal, topical, transdermal, rectal, subcutaneous, intradermal, intravenous, and intramuscular.