移植手术方案的细微调整改变了移植血管病变期间动脉壁的细胞结构。

Frontiers in transplantation Pub Date : 2024-04-29 eCollection Date: 2024-01-01 DOI:10.3389/frtra.2024.1260125
Laura Mickiewicz, Rana Zahreddine, Kévin Cormier, Sophie Peries, Arnaud Del Bello, Muriel Laffargue, Natalia F Smirnova
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引用次数: 0

摘要

简介移植血管病变(TV)是实体器官移植后的一种主要并发症,其特征是动脉内膜增厚,阻塞血管管腔,导致器官排斥反应。迄今为止,移植性动脉内膜病变在很大程度上仍无法治疗,这主要是因为其发病过程尚不清楚。用于模拟 TV 的小鼠主动脉移植依赖于高度可变的实验方案,尤其是用于连接供体主动脉和受体的吻合类型。虽然血管所受的创伤程度会显著影响病理结果,但吻合类型对小鼠 TV 的影响尚未得到详细研究:在这项研究中,我们比较了将 BALB/C 供体小鼠的主动脉移植物移植到 C57BL/6J 受体小鼠体内的细胞组成,采用了两种不同的吻合策略:套管式和袖带式:结果:虽然这两种模型在某些方面都再现了人类 TV 的情况,但移植物的细胞组成却存在显著差异。事实上,与袖套组相比,袖套组主动脉移植物的血管平滑肌细胞覆盖了更大的新内膜区域。袖套组的主动脉移植物含有较多的 T 细胞,而袖带组则有较多的 B 细胞浸润:这些数据共同表明,移植手术方案中看似微小的技术差异会在很大程度上影响移植物的细胞组成,进而影响小鼠主动脉移植后的TV机制。
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A minor tweak in transplant surgery protocols alters the cellular landscape of the arterial wall during transplant vasculopathy.

Introduction: Transplant vasculopathy (TV) is a major complication after solid organ transplantation, distinguished by an arterial intimal thickening that obstructs the vascular lumen and leads to organ rejection. To date, TV remains largely untreatable, mainly because the processes involved in its development remain unclear. Aortic transplantation in mice, used to mimic TV, relies on highly variable experimental protocols, particularly regarding the type of anastomosis used to connect the donor aorta to the recipient. While the amount of trauma undergone by a vessel can dramatically affect the resulting pathology, the impact of the type of anastomosis on TV in mice has not been investigated in detail.

Methods: In this study, we compare the cellular composition of aortic grafts from BALB/C donor mice transplanted into C57BL/6J recipient mice using two different anastomosis strategies: sleeve and cuff.

Results: While both models recapitulated some aspects of human TV, there were striking differences in the cellular composition of the grafts. Indeed, aortic grafts from the cuff group displayed a larger coverage of the neointimal area by vascular smooth muscle cells compared to the sleeve group. Aortic grafts from the sleeve group contained higher amounts of T cells, while the cuff group displayed larger B-cell infiltrates.

Discussion: Together, these data indicate that a seemingly minor technical difference in transplant surgery protocols can largely impact the cellular composition of the graft, and thus the mechanisms underlying TV after aortic transplantation in mice.

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