Monocyte Recruitment for Vascular Tissue Regeneration.

Monocyte Recruitment for Vascular Tissue Regeneration.
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DOI:
10.1002/adhm.202200890
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发表时间:
2022-11
影响因子:
10
通讯作者:
Andreadis, Stelios T.
Andreadis, Stelios T.
中科院分区:
工程技术1区
文献类型:
--
作者:
Nasiri, Bita;Yi, Tai;Wu, Yulun;Smith, Randall J.;Podder, Ashis Kumar;Breuer, Christopher K.;Andreadis, Stelios T.

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我们提出了一种策略,从血液中招募单核细胞(MC),从非接种(无细胞)组织工程血管移植物再生血管组织。当固定在血管移植物表面时,融合蛋白H2 R5可以在静态或流动条件下以切应力依赖的方式捕获血液来源的MC。结合的MC转变为表达M1和M2表型特异性基因的巨噬细胞(M β)。当将H2 R5功能化的A-TEV植入小鼠主动脉中时,它们保持开放并形成表达EC和MC特异性蛋白的连续内皮。在EC层下面,形成共表达平滑肌细胞(SMC)和MC特异性标志物的多个细胞层。使用新型CX 3CR 1-五彩纸屑小鼠模型进行的谱系追踪分析表明,植入后2周和4周,荧光标记的MC填充移植物管腔,为支持MC/MC向移植物管腔募集提供了直接证据。考虑到它们在血液中的丰度,循环MC可能是在正确的化学和生物力学线索下直接有助于无细胞血管移植物的内皮化和血管壁形成的细胞的重要来源。我们提出了一种新的策略,从血液中招募单核细胞(MC)再生无细胞动脉血管移植物。将血管移植物植入一种新型五彩纸屑小鼠模型表明,荧光标记的MC填充移植物管腔,提供直接证据支持MC招募。募集到移植物管腔的MC转变为内皮细胞和平滑肌细胞,产生功能性新生动脉。
We present a strategy to recruit monocytes (MC) from blood to regenerate vascular tissue from unseeded (cell-free) tissue engineered vascular grafts. When immobilized on the surface of vascular grafts, the fusion protein, H2R5 could capture blood derived MC under static or flow conditions in a shear stress dependent manner. The bound MC turned into macrophages (Mϕ) expressing both M1 and M2 phenotype specific genes. When H2R5 functionalized A-TEV were implanted into the mouse aorta, they remained patent and formed a continuous endothelium expressing both EC and MC specific proteins. Underneath the EC layer, multiple cells layers were formed co-expressing both smooth muscle cell (SMC) and MC specific markers. Lineage tracing analysis using a novel CX3CR1-confetti mouse model demonstrated that fluorescently labeled MC populated the graft lumen by two and four weeks post-implantation, providing direct evidence in support of MC/Mϕ recruitment to the graft lumen. Given their abundance in the blood, circulating MCs may be a great source of cells that contribute directly to the endothelialization and vascular wall formation of acellular vascular grafts under the right chemical and biomechanical cues. We present a novel strategy to recruit monocytes (MC) from blood to regenerate cell-free arterial vascular grafts. Implantation of vascular grafts into a novel confetti mouse model demonstrated that fluorescently labeled MC populated the graft lumen, providing direct evidence in support of MC recruitment. MC recruited to the graft lumen turned into endothelial and smooth muscle cells generating functional neoarteries.
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