Patient-derived endothelial progenitor cells improve vascular graft patency in a rodent model.
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 articleSubject
AnimalsBlood Vessel Prosthesis
Cells, Cultured
Endothelial Cells
Endothelium, Vascular
Humans
Hyperplasia
Male
Protein C
Rats
Rats, Nude
Stem Cells
Tunica Intima
Vascular Grafting
Vascular Patency
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https://hdl.handle.net/10161/10349Published Version (Please cite this version)
10.1016/j.actbio.2011.09.002Publication 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.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
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
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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