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Patient-derived endothelial progenitor cells improve vascular graft patency in a rodent model.

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Date
2012-01
Authors
Stroncek, JD
Ren, LC
Klitzman, B
Reichert, WM
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Abstract
Late outgrowth endothelial progenitor cells (EPCs) derived from the peripheral blood of patients with significant coronary artery disease were sodded into the lumens of small diameter expanded polytetrafluoroethylene (ePTFE) vascular grafts. Grafts (1mm inner diameter) were denucleated and sodded either with native EPCs or with EPCs transfected with an adenoviral vector containing the gene for human thrombomodulin (EPC+AdTM). EPC+AdTM was shown to increase the in vitro rate of graft activated protein C (APC) production 4-fold over grafts sodded with untransfected EPCs (p<0.05). Unsodded control and EPC-sodded and EPC+AdTM-sodded grafts were implanted bilaterally into the femoral arteries of athymic rats for 7 or 28 days. Unsodded control grafts, both with and without denucleation treatment, each exhibited 7 day patency rates of 25%. Unsodded grafts showed extensive thrombosis and were not tested for patency over 28 days. In contrast, grafts sodded with untransfected EPCs or EPC+AdTM both had 7 day patency rates of 88-89% and 28 day patency rates of 75-88%. Intimal hyperplasia was observed near both the proximal and distal anastomoses in all sodded graft conditions but did not appear to be the primary occlusive failure event. This in vivo study suggests autologous EPCs derived from the peripheral blood of patients with coronary artery disease may improve the performance of synthetic vascular grafts, although no differences were observed between untransfected EPCs and TM transfected EPCs.
Type
Journal article
Subject
Animals
Blood Vessel Prosthesis
Cells, Cultured
Endothelial Cells
Endothelium, Vascular
Humans
Hyperplasia
Male
Protein C
Rats
Rats, Nude
Stem Cells
Tunica Intima
Vascular Grafting
Vascular Patency
Permalink
https://hdl.handle.net/10161/10349
Published Version (Please cite this version)
10.1016/j.actbio.2011.09.002
Publication Info
Stroncek, JD; Ren, LC; Klitzman, B; & Reichert, WM (2012). Patient-derived endothelial progenitor cells improve vascular graft patency in a rodent model. Acta Biomater, 8(1). pp. 201-208. 10.1016/j.actbio.2011.09.002. Retrieved from https://hdl.handle.net/10161/10349.
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Scholars@Duke

Klitzman

Bruce Klitzman

Associate Professor Emeritus in Surgery
Our overriding interests are in the fields of tissue engineering, wound healing, biosensors, and long term improvement of medical device implantation. My basic research interests are in the area of physiological mechanisms of optimizing substrate transport to tissue. This broad topic covers studies on a whole animal, whole organ, hemorheological, microvascular, cellular, ultrastructural, and molecular level. The current projects include: 1) control of blood flow and flow distribu
Reichert

William M. Reichert

Professor Emeritus of Biomedical Engineering
Adjunct Professor of Biomedical Sciences, Makerere University, Kampala, Uganda (pending)Director of the Duke-Makerere BME PartnershipDr. Reichert's research interests have included biosensors, protein mediated cell adhesion, wound healing, and biocompatibilty.  Dr. Reichert was the first member of the engineering faculty to receive the Clemson Award from the Society for Biomaterials (there have since been three others) and elected as a Fellow of the International Unio
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