Mesenchymal stromal exosome-functionalized scaffolds induce innate and adaptive immunomodulatory responses toward tissue repair.

Mesenchymal stromal exosome-functionalized scaffolds induce innate and adaptive immunomodulatory responses toward tissue repair.
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间充质基质外泌体功能化支架诱导针对组织修复的先天性和适应性免疫调节反应

DOI:
10.1126/sciadv.abf7207
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发表时间:
2021-05
期刊:
影响因子:
13.6
通讯作者:
Luo Y
Luo Y
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Su N;Hao Y;Wang F;Hou W;Chen H;Luo Y

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新的载有外泌体的支架揭示了有利于组织修复的免疫细胞活动。设计能够诱导和引导适当的免疫反应的支架有望用于组织修复/再生。生物功能支架在此通过将间充质基质外泌体固定到纤维聚酯材料上来制备,并允许细胞介导的膜结合囊泡的递送。定量细胞水平分析显示,免疫细胞在体内主导从支架中摄取外泌体,材料和外泌体分别充当免疫细胞的招募者和训练者,以协同促进小鼠皮肤伤口中有益的巨噬细胞和调节性T细胞反应。在远程免疫器官中发现了适应性T辅助细胞反应,并且载有外泌体的支架促进了大型皮肤损伤模型中的组织修复。这项研究证明了生物植入物的局部和全身免疫反应的重要机制,了解组织修复免疫调节可能会指导新的生物功能支架的设计。
New exosome-laden scaffolds shed light on the immune cell activities that benefit tissue repair. Designing scaffolds capable of inducing and guiding appropriate immune responses holds promise for tissue repair/regeneration. Biofunctional scaffolds were here prepared by immobilizing mesenchymal stromal exosomes onto fibrous polyester materials and allowed cell-mediated delivery of membrane-bound vesicles. Quantitative cell-level analyses revealed that immune cells dominated the uptake of exosomes from scaffolds in vivo, with materials and exosomes acting as the recruiter and trainer for immune cells, respectively, to synergistically promote beneficial macrophage and regulatory T cell responses in skin wounds in mice. Adaptive T helper cell responses were found active in remote immune organs, and exosome-laden scaffolds facilitated tissue repair in large skin injury models. This study demonstrated important mechanisms involved in local and systemic immune responses to biological implants, and understanding tissue-reparative immunomodulation may guide the design of new biofunctional scaffolds.
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