Tissue Engineered Vascular Graft Recipient Interleukin 10 Status Is Critical for Preventing Thrombosis.

Tissue Engineered Vascular Graft Recipient Interleukin 10 Status Is Critical for Preventing Thrombosis.
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DOI:
10.1002/adhm.202001094
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发表时间:
2020-12
影响因子:
10
通讯作者:
Breuer CK
Breuer CK
中科院分区:
工程技术1区
文献类型:
--
作者:
Mirhaidari GJM;Barker JC;Zbinden JC;Santantonio BM;Chang YC;Best CA;Reinhardt JW;Blum KM;Yi T;Breuer CK

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组织工程血管移植(TEVGs)是一项很有前途的技术,但受到闭塞的阻碍。用骨髓来源的单核细胞(BM-MNCs)播种可减轻闭塞,但确切的机制尚不清楚。种子细胞迅速消失,并可能通过旁分泌信号介导抗炎作用。在这里,我们报道了一系列互惠的遗传TEVG植入和重组蛋白处理,以研究宿主和种子细胞中白细胞介素-10(一种抗炎细胞因子)的作用。将野生型和IL-10小鼠的BM-MNCs植入tevg,再加上未播种的移植物,植入野生型和IL-10小鼠。未经种子移植的野生型小鼠也接受重组IL-10。连续超声评估闭塞性,14天收集tevg进行免疫组织化学分析。由于急性(<3天)血栓形成,IL-10 KO小鼠的TEVGs闭塞发生率明显高于野生型小鼠。细胞播种在IL-10 KO小鼠中拯救tevg,与野生型开放相当。来自宿主和种子细胞的IL-10对移植物炎症和巨噬细胞表型没有显著影响,但IL-10处理显示出有趣的生物学效应,包括降低细胞增殖和增加M2巨噬细胞极化。来自宿主的IL-10对预防TEVG血栓形成至关重要,种子BM-MNCs在IL-10 KO小鼠中具有显著的抗血栓作用。
Tissue engineered vascular grafts (TEVGs) are a promising technology, but are hindered by occlusion. Seeding with bone-marrow derived mononuclear cells (BM-MNCs) mitigates occlusion, yet the precise mechanism remains unclear. Seeded cells disappear quickly and potentially mediate an anti-inflammatory effect through paracrine signaling. Here, we report a series of reciprocal genetic TEVG implantations plus recombinant protein treatment to investigate what role interleukin-10, an anti-inflammatory cytokine, plays from both host and seeded cells. TEVGs seeded with BM-MNCs from wild-type and IL-10 KO mice, plus unseeded grafts, were implanted into wild-type and IL-10 KO mice. Wild-type mice with unseeded grafts also received recombinant IL-10. Serial ultrasound evaluated occlusion and TEVGs were harvested at 14 days for immunohistochemical analysis. TEVGs in IL-10 KO mice had significantly higher occlusion incidence compared to wild-type mice attributed to acute (<3day) thrombosis. Cell seeding rescued TEVGs in IL-10 KO mice comparable to wild-type patency. IL-10 from the host and seeded cells did not significantly influence graft inflammation and macrophage phenotype, yet IL-10 treatment showed interesting biologic effects including decreasing cell proliferation and increasing M2 macrophage polarization. IL-10 from the host is critical for preventing TEVG thrombosis and seeded BM-MNCs exert a significant anti-thrombotic effect in IL-10 KO mice.
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