DEVELOPMENT OF AN ENDOTHELIAL-CELL-SEEDING MATRIX

THERE ARE 300,000 CORONARY ANGIOPLASTY PROCEDURES PERFORMED ANNUALLY. OF THESE, 12 TO 34 PERCENT OF THE CASES CONSISTENTLY RESULT IN RESTENOSIS AND THE NEED TO REOPEN OR BYPASS THE OCCLUDED PORTION OF THE VESSEL. ONE OF THE PRIMARY CAUSES OF RESTENOSIS IS THE ACCUMULATION OF PLATELETS IN THE AREA DENUDED BY ANGIOPLASTY, WHICH IN TURN PRODUCE PLATELET-DERIVED GROWTH FACTOR, A STRONG CHEMOATTRACTANT FOR SMOOTH MUSCLE CELLS. THE ACCUMULATION OF SMOOTH MUSCLE CELLS LEADS TO HYPERPLASIA ANDULTIMATELY TO OCCLUSION OF THE VESSEL. THIS RESEARCH IS DIRECTED AT DEVELOPING A SYSTEM TO RE-SEED THE DENUDED PORTION OF THE VESSEL WITH AUTOLOGOUS ENDOTHELIAL CELLS TO CIRCUMVENT THE ACCUMULATION OF PLATELETS. THIS WILL BE DONE BY DEVELOPING A CELL-SEEDING MATRIX DESIGNED TO SUSPEND CELLS IN DURING THE SEEDING PROCESS AND A CELL DELIVERY SYSTEM. THE DEVELOPED MATRIX AND DELIVERY SYSTEM WILL BE TESTED IN AN IN VITRO PERFUSION LOOP (PHASE I), FOLLOWED BY IN VIVO APPLICATION (PHASE II) IN A DENUDED CANINE ARTERY. THIS WILL REQUIRE DEVELOPING A SEEDING MATRIX THAT WILL ENHANCE CELL ATTACHMENT TO THE DENUDED VESSEL AND TESTING THE CELL-SEEDING SYSTEM FOR DELIVERY OF THE CELLS TO THE DENUDEDVESSEL.