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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.

SUBMITTER: Stroncek JD

PROVIDER: S-EPMC3226906 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature

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

Stroncek J D JD Ren L C LC Klitzman B B Reichert W M WM

Acta biomaterialia 20110906 1

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 pr ...[more]

PMID: 21945828

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Project description:BACKGROUND:In this single-center, retrospective observational study, we assessed the long-term patency of vascular access (VA) after first VA placement to uncover independent risk factors associated with VA patency in Asian hemodialysis (HD) patients stratified by age. We also investigated factors associated with VA patency among older HD patients according to the type of VA in the overall study population. METHODS:The study period was from January 2011 to December 2013. A total of 651 chronic HD patients with confirmed first upper-extremity VA placement were enrolled, and their records were analyzed retrospectively. A total of 445 patients (68.4%) made up the nonelderly group (<?65?years), and 206 patients (31.6%) were in the elderly group (? 65?years). Study outcomes were defined as primary or secondary VA patency. RESULTS:Autologous arteriovenous fistula (AVF) was more common in the nonelderly group (P?<? 0.01). Kaplan-Meier curve survival analysis indicated that primary patency was longer in the nonelderly group (P?<? 0.01); secondary patency, however, was similar between groups (P?=?0.37). The multivariate analysis of factors associated with primary VA patency revealed that increased age (hazard ratio [HR], 1.02; 95% confidence interval [CI], 1.01-1.03; P?<? 0.01) was associated with shorter primary patency, and AVF (HR, 0.38; 95% CI, 0.28-0.51; P?<? 0.01) was associated with longer primary patency. AVF (HR, 0.57; 95% CI, 0.37-0.87; P?=?0.010) and diabetes mellitus (HR, 1.56; 95% CI, 1.07-2.29; P?=?0.02) were independently associated with longer and shorter secondary patency periods, respectively; however, increased age was not a risk factor for decreased secondary patency. CONCLUSIONS:Increased age was associated with shorter primary patency but not secondary patency, whereas AVF placement was associated with longer primary and secondary patency. Considering the similar rates of secondary patency between groups and the superior patency of AVF compared to arteriovenous graft, a fistula-first strategy should be applied to appropriate older patients.

Dataset Information

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

Publications

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

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