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Bone marrow-derived mononuclear cell seeded bioresorbable vascular graft improves acute graft patency by inhibiting thrombus formation via platelet adhesion.

ABSTRACT: Acute thrombosis is a crucial cause of bioresorbable vascular graft (BVG) failure. Bone marrow-derived mononuclear cell (BM-MNC)-seeded BVGs demonstrated high graft patency, however, the effect of seeded BM-MNCs against thrombosis remains to be elucidated. Thus, we evaluated an antithrombotic effect of BM-MNC-seeding and utilized platelet-depletion mouse models to evaluate the contribution of platelets to acute thrombosis of BVGs.BVGs were composed of poly(glycolic acid) mesh sealed with poly(l-lactideco-?-caprolactone). BM-MNC-seeded BVGs and unseeded BVGs were implanted to wild type C57BL/6 mice (n?=?10/group) as inferior vena cava interposition conduits. To evaluate platelet effect on acute thrombosis, c-Mpl-/- mice and Pf4-Cre+; iDTR mice with decreased platelet number were also implanted with unseeded BVGs (n?=?10/group). BVG patency was evaluated at 2, 4, and 8?weeks by ultrasound. BM-MNC-seeded BVGs demonstrated a significantly higher patency rate than unseeded BVGs during the acute phase (2-week, 90% vs 30%, p?=?.020), and patency rates of these grafts were sustained until week 8. Similar to BM-MNC-seeded BVGs, C-Mpl-/- and Pf4-Cre+; iDTR mice also showed favorable graft patency (2-week, 90% and 80%, respectively) during the acute phase. However, the patency rate of Pf4-Cre+; iDTR mice decreased gradually after DTR treatment as platelet number recovered to baseline. An in vitro study revealed BM-MNC-seeding significantly inhibited platelet adhesion to BVGs compared to unseeded BVGs, (1.75?±?0.45 vs 8.69?±?0.68?×?103?platelets/mm2, p?

SUBMITTER: Miyachi H

PROVIDER: S-EPMC6061926 | biostudies-other | 2018 Sep

REPOSITORIES: biostudies-other

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Bone marrow-derived mononuclear cell seeded bioresorbable vascular graft improves acute graft patency by inhibiting thrombus formation via platelet adhesion.

Miyachi Hideki H Reinhardt James W JW Otsuru Satoru S Tara Shuhei S Nakayama Hidetaka H Yi Tai T Lee Yong-Ung YU Miyamoto Shinka S Shoji Toshihiro T Sugiura Tadahisa T Breuer Christopher K CK Shinoka Toshiharu T

International journal of cardiology 20180901

<h4>Background</h4>Acute thrombosis is a crucial cause of bioresorbable vascular graft (BVG) failure. Bone marrow-derived mononuclear cell (BM-MNC)-seeded BVGs demonstrated high graft patency, however, the effect of seeded BM-MNCs against thrombosis remains to be elucidated. Thus, we evaluated an antithrombotic effect of BM-MNC-seeding and utilized platelet-depletion mouse models to evaluate the contribution of platelets to acute thrombosis of BVGs.<h4>Methods and results</h4>BVGs were composed ...[more]

PMID: 29887474

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Project description:BackgroundArteriovenous graft stenosis leading to thrombosis is a major cause of complications in patients undergoing hemodialysis. Procedural interventions may restore patency but are costly. Although there is no proven pharmacologic therapy, dipyridamole may be promising because of its known vascular antiproliferative activity.MethodsWe conducted a randomized, double-blind, placebo-controlled trial of extended-release dipyridamole, at a dose of 200 mg, and aspirin, at a dose of 25 mg, given twice daily after the placement of a new arteriovenous graft until the primary outcome, loss of primary unassisted patency (i.e., patency without thrombosis or requirement for intervention), was reached. Secondary outcomes were cumulative graft failure and death. Primary and secondary outcomes were analyzed with the use of a Cox proportional-hazards regression with adjustment for prespecified covariates.ResultsAt 13 centers in the United States, 649 patients were randomly assigned to receive dipyridamole plus aspirin (321 patients) or placebo (328 patients) over a period of 4.5 years, with 6 additional months of follow-up. The incidence of primary unassisted patency at 1 year was 23% (95% confidence interval [CI], 18 to 28) in the placebo group and 28% (95% CI, 23 to 34) in the dipyridamole-aspirin group, an absolute difference of 5 percentage points. Treatment with dipyridamole plus aspirin significantly prolonged the duration of primary unassisted patency (hazard ratio, 0.82; 95% CI, 0.68 to 0.98; P=0.03) and inhibited stenosis. The incidences of cumulative graft failure, death, the composite of graft failure or death, and serious adverse events (including bleeding) did not differ significantly between study groups.ConclusionsTreatment with dipyridamole plus aspirin had a significant but modest effect in reducing the risk of stenosis and improving the duration of primary unassisted patency of newly created grafts. (ClinicalTrials.gov number, NCT00067119.)

Project description:ObjectiveTherapeutic anticoagulation (AC) is used clinically for prolongation of infrainguinal bypass patency, but evidence for the efficacy of this practice is conflicting. The objective of our study was to determine the association of AC with bypass graft primary patency.MethodsClinical and comorbid data of patients undergoing infrainguinal bypass grafts to a below-knee target with at least 1 year of follow-up performed from 2003 to 2015 were obtained from the Society for Vascular Surgery Vascular Quality Initiative. Inverse propensity of treatment-weighted Cox regression was used to assess the effect of AC on patency in the total cohort while adjusting for clinical, operative, and comorbid differences between treatment groups. Subgroup analyses of distal targets and conduit type were performed. Perioperative complications were analyzed using propensity-weighted logistic regression.ResultsWe identified 7612 bypass grafts with intact 1-year follow-up information from 2003 to 2015. The mean age was 67.5 ± 11.2 years; 30.5% (n = 2320) were female, and 28.6% (n = 2165) were discharged on therapeutic AC. The anticoagulated group had a higher rate of tibial, ankle, and pedal targets (52.1% [n = 1127] vs 47.6% [n = 2269]; P < .001), had a greater use of non-single-segment vein conduits (44.3% [n = 951] vs 26.5% [n = 1426]; P < .001), and was more likely to have had a previous ipsilateral bypass (27.2% [n = 589] vs 14.7% [n = 794]; P < .001) or stent (25.4% [n = 550] vs 20.9% [n = 1130]; P < .001). Estimated unadjusted primary patency was 70.8% ± 0.6% at 1 year and lower for anticoagulated bypasses (66.9% ± 1.2% vs 72.4% ± 0.7%; P < .001). Propensity-weighted analysis showed no significant association of AC with primary patency in the overall cohort (hazard ratio [HR], 0.98; 95% confidence interval [CI], 0.86-1.11; P = .8) but demonstrated a trend toward improvement of primary patency in those with a non-single-segment vein conduit to a below-knee popliteal target (HR, 0.85; 95% CI, 0.80-1.02; P = .09). AC was associated with significantly improved secondary patency in those with prosthetic bypass grafts (HR, 0.77; 95% CI, 0.62-0.96; P = .02) or prosthetic bypasses to an infrapopliteal target (HR, 0.72; 95% CI, 0.54-0.97; P = .02). Odds of postoperative wound complications were significantly higher in those receiving AC (odds ratio, 1.33; 95% CI, 1.11-1.61; P = .002).ConclusionsThis study does not demonstrate a significant impact of therapeutic AC on primary patency for infrainguinal bypass grafts. Treatment with AC may benefit secondary patency in those with a prosthetic bypass, especially to an infrapopliteal target, but at an increased risk of postoperative wound complications.

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Dataset Information

Bone marrow-derived mononuclear cell seeded bioresorbable vascular graft improves acute graft patency by inhibiting thrombus formation via platelet adhesion.

Publications

Bone marrow-derived mononuclear cell seeded bioresorbable vascular graft improves acute graft patency by inhibiting thrombus formation via platelet adhesion.

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