Netrin‐1 Promotes Inflammation Resolution to Achieve Endothelialization of Small‐Diameter Tissue Engineering Blood Vessels by Improving Endothelial Progenitor Cells Function In Situ,Advanced Science

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Netrin‐1 Promotes Inflammation Resolution to Achieve Endothelialization of Small‐Diameter Tissue Engineering Blood Vessels by Improving Endothelial Progenitor Cells Function In Situ
Advanced Science ( IF 14.3 ) Pub Date : 2017-09-28 , DOI: 10.1002/advs.201700278
Yanzhao Li ₁ , Simin Wan ₁ , Ge Liu ₁ , Wang Cai ₁ , Da Huo ₁ , Gang Li ₁ , Mingcan Yang ₁ , Yuxin Wang ₁ , Ge Guan ₁ , Ning Ding ₁ , Feila Liu ₁ , Wen Zeng ₁ , Chuhong Zhu ₁

Affiliation

The transplant of small‐diameter tissue engineering blood vessels (small‐diameter TEBVs) (<6 mm) in vascular replacement therapy often fails because of early onset thrombosis and long‐standing chronic inflammation. The specific inflammation state involved in small‐diameter TEBVs transplants remains unclear, and whether promoting inflammation resolution would be useful for small‐diameter TEBVs therapy need study. The neural protuberant orientation factor 1 (Netrin‐1) is found present in endothelial cells of natural blood vessels and has anti‐inflammatory effects. This work generates netrin‐1‐modified small‐diameter TEBVs by using layer‐by‐layer self‐assembly to resolve the inflammation. The results show that netrin‐1 reprograms macrophages (MΦ) to assume an anti‐inflammatory phenotype and promotes the infiltration and subsequent efflux of MΦ from inflamed sites over time, which improves the local microenvironment and the function of early homing endothelial progenitor cells (EPCs). Small‐diameter TEBVs modified by netrin‐1 achieve endothelialization after 30 d and retain patency at 14 months. These findings suggest that promoting the resolution of inflammation in time is necessary to induce endothelialization of small‐diameter TEBVs and prevent early thrombosis and problems associated with chronic inflammation. Furthermore, this work finds that the MΦ‐derived exosomes can target and regulate EPCs, which may serve as a useful treatment for other inflammatory diseases.

中文翻译：

Netrin-1 通过改善原位内皮祖细胞功能促进炎症消退，实现小直径组织工程血管的内皮化

血管替代治疗中的小直径组织工程血管（小直径TEBV）（<6 mm）移植常常因早期发生的血栓形成和长期慢性炎症而失败。小直径 TEBV 移植涉及的具体炎症状态仍不清楚，促进炎症消退是否对小直径 TEBV 治疗有用还需要研究。神经突起定向因子 1 (Netrin-1) 存在于天然血管的内皮细胞中，具有抗炎作用。这项工作通过使用逐层自组装来生成 netrin-1 修饰的小直径 TEBV 以解决炎症。结果表明，netrin-1对巨噬细胞（MΦ）进行重编程，使其呈现抗炎表型，并随着时间的推移促进MΦ从炎症部位浸润和随后流出，从而改善局部微环境和早期归巢内皮祖细胞（EPC）的功能）。经过 netrin-1 修饰的小直径 TEBV 在 30 天后实现内皮化，并在 14 个月时保持通畅。这些发现表明，及时促进炎症消退对于诱导小直径 TEBV 内皮化并预防早期血栓形成和与慢性炎症相关的问题是必要的。此外，这项工作发现 MΦ 衍生的外泌体可以靶向和调节 EPC，这可能成为其他炎症性疾病的有效治疗方法。

更新日期：2017-09-28

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