Abstract
BackgroundCoronary bypass graft failure as a result of acute thrombosis and intimal hyperplasia has been the major challenge in surgical procedures involving small-diameter vascular prosthesis. Coating synthetic grafts with patients' own endothelial cells has been suggested to improve the patency rate and overall success of bypass surgeries.Methodology/Principal FindingsWe isolated endothelial progenitor cells (EPCs) from leftover pieces of human saphenous vein/mammary artery. We demonstrate that EPCs can be expanded to generate millions of cells under low-density culture conditions. Exposure to high-density conditions induces differentiation to endothelial cell phenotype. EPC–derived endothelial cells show expression of CD144high, CD31, and vWF. We then assessed the ability of differentiated endothelial cells to adhere and grow on small diameter expanded polytetrafluoroethylene (ePTFE) tubings. Since ePTFE tubings are highly hydrophobic, we optimized protocols to introduce hydrophilic groups on luminal surface of ePTFE tubings. We demonstrate here a stepwise protocol that involves introduction of hydrophilic moieties and coating with defined ECM components that support adhesion of endothelial cells, but not of blood platelets.Conclusion/SignificanceOur data confirms that endothelial progenitors obtained from adult human blood vessels can be expanded in vitro under xenoprotein-free conditions, for potential use in endothelialization of small diameter ePTFE grafts. These endothelialized grafts may represent a promising treatment strategy for improving the clinical outcome of small-caliber vascular grafts in cardiac bypass surgeries.
Highlights
Coronary artery disease is the most prevalent heart disease that occurs because of stenosis/narrowing and blockage of coronary arteries, restricting the blood flow to myocardium
coronary artery bypass graft (CABG) involves surgical removal of blood vessels from patient’s body and grafting this to the coronary arteries so as to bypass the atherosclerotic narrowing in order to improve blood supply to the myocardium. Both percutaneous coronary interventions (PCI) and CABG are more effective than medical management at relieving coronary artery disease [2,3,4] but CABG is considered superior to PCI in multi-vessel coronary disease treatment with lower rates of death, myocardial infarction and repeat revascularization [5]
The low density culture protocol helps in generating larger number of CD133+ endothelial population from initially fewer CD133+ endothelial progenitor cells; EPCs (Figure S1)
Summary
Coronary artery disease is the most prevalent heart disease that occurs because of stenosis/narrowing and blockage of coronary arteries, restricting the blood flow to myocardium (heart muscles). Surface modification of ePTFE tubes so as to make them suitable for adhesion and growth of autologous endothelial cells for better endothelialization and patency of ePTFE grafts has been examined in various in vitro and in vivo models [10,11,12,13]. Though such synthetic vascular grafts are non-immunogenic they demonstrate increased platelet aggregation/thrombosis and stenosis as compared to autologous vessels, especially when their diameter is small [14]. Coating synthetic grafts with patients’ own endothelial cells has been suggested to improve the patency rate and overall success of bypass surgeries
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