Nidogen1-enriched extracellular vesicles accelerate angiogenesis and bone regeneration by targeting Myosin-10 to regulate endothelial cell adhesion.

Nidogen1-enriched extracellular vesicles accelerate angiogenesis and bone regeneration by targeting Myosin-10 to regulate endothelial cell adhesion.
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富含 Nidogen1 的细胞外囊泡通过靶向 Myosin-10 调节内皮细胞粘附来加速血管生成和骨再生

DOI:
10.1016/j.bioactmat.2021.10.021
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发表时间:
2022-06
影响因子:
18.9
通讯作者:
Yang L
Yang L
中科院分区:
工程技术1区
文献类型:
--
作者:
Cheng P;Cao T;Zhao X;Lu W;Miao S;Ning F;Wang D;Gao Y;Wang L;Pei G;Yang L

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组织工程骨修复大段骨缺损的技术瓶颈是组织工程骨的血管化。虽然有研究表明,骨髓间充质干细胞(BMSCs)来源的细胞外囊泡(EVs)通过促进血管生成促进骨愈合和修复,但其效应分子和机制尚不清楚,未能为未来无细胞干预的研究和开发提供思路。在这里,我们发现,Nidogen 1富集EV(EV-NID 1)来自骨髓间充质干细胞干扰的形成和组装的粘着斑(FA)通过靶向肌球蛋白-10,从而降低大鼠动脉内皮细胞(RAECs)的粘附强度细胞外基质(ECM),并提高RAECs的迁移和血管生成的潜力。此外,通过与复合水凝胶一起递送,EV-NID 1被证明可以促进大鼠股骨缺损中的血管生成和骨再生。本研究确定了EV-NID 1的细胞内结合靶点,并进一步阐明了一种新的方法和机制,从而为血管化组织工程产品的开发提供了一种具有精确靶点的无细胞构建策略。Nidogen 1富集在来源于BMSC的细胞外囊泡(EV-NID 1)中。EV-NID 1干扰局灶性粘连(FA)的形成和组装。肌球蛋白-10被鉴定为EV-NID 1的细胞内结合靶点。负载EV-NID 1的复合水凝胶通过加速血管生成促进骨缺损的修复。
The technique bottleneck of repairing large bone defects with tissue engineered bone is the vascularization of tissue engineered grafts. Although some studies have shown that extracellular vesicles (EVs) derived from bone marrow mesenchymal stem cells (BMSCs) promote bone healing and repair by accelerating angiogenesis, the effector molecules and the mechanism remain unclear, which fail to provide ideas for the future research and development of cell-free interventions. Here, we found that Nidogen1-enriched EV (EV-NID1) derived from BMSCs interferes with the formation and assembly of focal adhesions (FAs) by targeting myosin-10, thereby reducing the adhesion strength of rat arterial endothelial cells (RAECs) to the extracellular matrix (ECM), and enhancing the migration and angiogenesis potential of RAECs. Moreover, by delivery with composite hydrogel, EV-NID1 is demonstrated to promote angiogenesis and bone regeneration in rat femoral defects. This study identifies the intracellular binding target of EV-NID1 and further elucidates a novel approach and mechanism, thereby providing a cell-free construction strategy with precise targets for the development of vascularized tissue engineering products. Nidogen1 is enriched in extracellular vesicles (EV-NID1) derived from BMSCs. EV-NID1 interferes with the formation and assembly of focal adhesions (FAs). Myosin-10 was identified as the intracellular binding target of EV-NID1. The composite hydrogel loaded with EV-NID1 promotes the repair of bone defects by accelerating angiogenesis.
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