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Decellularised Human Umbilical Artery as a Vascular Graft Elicits Minimal Pro-Inflammatory Host Response Ex Vivo and In Vivo.

ABSTRACT: Small diameter (<6 mm) vessel grafts still pose a challenge for scientists worldwide. Decellularised umbilical artery (dUA) remains promising as small diameter tissue engineered vascular graft (TEVG), yet their immunogenicity remains unknown. Herein, we evaluated the host immune responses, with a focus on the innate part, towards human dUA implantation in mice, and confirmed our findings in an ex vivo allogeneic human setup. Overall, we did not observe any differences in the number of circulating white blood cells nor the number of monocytes among three groups of mice (1) dUA patch; (2) Sham; and (3) Mock throughout the study (day -7 to 28). Likewise, we found no difference in systemic inflammatory and anti-inflammatory cytokine levels between groups. However, a massive local remodelling response with M2 macrophages were observed in the dUA at day 28, whereas M1 macrophages were less frequent. Moreover, human monocytes from allogeneic individuals were differentiated into macrophages and exposed to lyophilised dUA to maximize an eventual M1 response. Yet, dUA did not elicit any immediate M1 response as determined by the absence of CCR7 and CXCL10. Together this suggests that human dUA elicits a minimal pro-inflammatory response further supporting its use as a TEVG in an allogeneic setup.

SUBMITTER: Ahlmann AH

PROVIDER: S-EPMC8347020 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:The internal mammary artery (IMA) is the preferred conduit for bypassing the left anterior descending (LAD) artery in patients undergoing coronary artery bypass grafting. Systematic evaluation of the frequency and predictors of IMA failure and long-term outcomes is lacking. METHODS AND RESULTS:The Project of Ex-vivo Vein Graft Engineering via Transfection (PREVENT) IV trial participants who underwent IMA-LAD revascularization and had 12- to 18-month angiographic follow-up (n=1539) were included. Logistic regression with fast false selection rate methods was used to identify characteristics associated with IMA failure (?75% stenosis). The relationship between IMA failure and long-term outcomes, including death, myocardial infarction, and repeat revascularization, was assessed with Cox regression. IMA failure occurred in 132 participants (8.6%). Predictors of IMA graft failure were LAD stenosis <75% (odds ratio, 1.76; 95% confidence interval, 1.19-2.59), additional bypass graft to diagonal branch (odds ratio, 1.92; 95% confidence interval, 1.33-2.76), and not having diabetes mellitus (odds ratio, 1.82; 95% confidence interval, 1.20-2.78). LAD stenosis and additional diagonal graft remained predictive of IMA failure in an alternative model that included angiographic failure or death before angiography as the outcome. IMA failure was associated with a significantly higher incidence of subsequent acute (<14 days of angiography) clinical events, mostly as a result of a higher rate of repeat revascularization. CONCLUSIONS:IMA failure was common and associated with higher rates of repeat revascularization, and patients with intermediate LAD stenosis or with an additional bypass graft to the diagonal branch had increased risk for IMA failure. These findings raise concerns about competitive flow and the benefit of coronary artery bypass grafting in intermediate LAD stenosis without functional evidence of ischemia. CLINICAL TRIAL REGISTRATION:URL: http:/www.clinicaltrials.gov. Unique identifier: NCT00042081.

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Decellularised Human Umbilical Artery as a Vascular Graft Elicits Minimal Pro-Inflammatory Host Response Ex Vivo and In Vivo.

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