The innate immune system contributes to tissue-engineered vascular graft performance
The innate immune system contributes to tissue-engineered vascular graft performance
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DOI：
10.1096/fj.14-268334
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发表时间：
2015-06-01
期刊：
影响因子：
4.8
通讯作者：
Breuer, Christopher
中科院分区：
文献类型：
--
作者：
Hibino, Narutoshi;Mejias, Dane;Breuer, Christopher
组织工程血管移植物（TEVG）的第一次临床试验确定狭窄是移植失败的主要原因。在这项研究中，我们的目的是阐明宿主免疫反应的作用，在狭窄的发展，使用小鼠模型的TEVG植入。我们发现，C.B-17野生型（WT）小鼠（对照）发生了显著的狭窄反应，而在免疫缺陷的SCID/米色（bg）变体中几乎完全消失。由于缺乏T和B淋巴细胞而缺乏适应性免疫系统的SCID小鼠经历了与WT对照相当的狭窄率（平均管腔直径，WT：0.071 +/- 0.035 mm，SCID：0.137 +/- 0.032 mm，SCID/bg：0.804 +/- 0.039 mm; P < 0.001）。bg突变的特征是NK细胞和血小板功能障碍，WT小鼠接受NK细胞中和（抗NK 1.1抗体）或抗血小板（阿司匹林/血小板[硫酸氢氯吡格雷]; Asp/Pla）治疗后，获得的通畅率几乎是SCID/bg小鼠的一半（NK Ab：0.356 +/- 0.151 mm，Asp/Pla：0.452 +/- 0.130 mm）。支架植入引起SCID/bg小鼠的免疫反应减弱，如TEVG外植体中巨噬细胞数量和促炎细胞因子mRNA表达所示。提示最初的先天性免疫反应是移植物狭窄的一个关键因素，这可能为第二代TEVG的预后和治疗提供一种策略。
The first clinical trial of tissue-engineered vascular grafts (TEVGs) identified stenosis as the primary cause of graft failure. In this study, we aimed to elucidate the role of the host immune response in the development of stenosis using a murine model of TEVG implantation. We found that the C.B-17 wild-type (WT) mouse (control) undergoes a dramatic stenotic response, which is nearly completely abolished in the immunodeficient SCID/beige (bg) variant. SCID mice, which lack an adaptive immune system due to the absence of T and B lymphocytes, experienced rates of stenosis comparable to WT controls (average luminal diameter, WT: 0.071 +/- 0.035 mm, SCID: 0.137 +/- 0.032 mm, SCID/bg: 0.804 +/- 0.039 mm; P < 0.001). The bg mutation is characterized by NK cell and platelet dysfunction, and systemic treatment of WT mice with either NK cell-neutralizing (anti-NK 1.1 antibody) or antiplatelet (aspirin/Plavix [clopidogrel bisulfate]; Asp/Pla) therapy achieved nearly half the patency observed in the SCID/bg mouse (NK Ab: 0.356 +/- 0.151 mm, Asp/Pla: 0.452 +/- 0.130 mm). Scaffold implantation elicited a blunted immune response in SCID/bg mice, as demonstrated by macrophage number and mRNA expression of proinflammatory cytokines in TEVG explants. Implicating the initial innate immune response as a critical factor in graft stenosis may provide a strategy for prognosis and therapy of second-generation TEVGs.