BMSC-derived extracellular matrix better optimizes the microenvironment to support nerve regeneration.
BMSC-derived extracellular matrix better optimizes the microenvironment to support nerve regeneration.
复制标题
BMSC 衍生的细胞外基质更好地优化微环境以支持神经再生。
DOI：
10.1016/j.biomaterials.2021.121251
复制
发表时间：
2022
期刊：
影响因子：
14
通讯作者：
Gu Yun
中科院分区：
文献类型：
--
作者：
Wang Shengran;Zhu Changlai;Zhang Bin;Hu Junxia;Xu Jinghui;Xue Chengbin;Bao Shuangxi;Gu Xiaokun;Ding Fei;Yang Yumin;Gu Xiaosong;Gu Yun
良好的微环境在神经再生中起着重要作用。来源于培养细胞或天然组织的细胞外基质（ECM）可以在各种微环境因素（包括生物化学、空间和生物力学因素）的存在下促进神经再生。本研究通过蛋白质组学和三维图像分析，确定由骨髓间充质细胞（BMSCs）分泌的ECM的组分和空间组织比来自雪旺细胞（SC），皮肤来源的前体雪旺细胞（SKP-SC）或成纤维细胞（FB）的ECM更类似于无细胞神经。ECM修饰的神经移植物（ECM-NG）通过将BMSC、SC、FB、SKP-SC与用于桥接神经缺损的精心设计的神经移植物共培养而工程化。基于组织学、神经生理学和行为学分析，BMSC-ECM-NG表现出最有前途的神经修复特性。由ECM-NG形成的再生微环境也具有蛋白质组学特征，并且BMSC-ECM-NG的优势通过与神经再生相关的因子的增强表达和降低的免疫应答来证明。总之，这些发现表明，BMSC衍生的ECM为神经再生创造了比其他ECM更上级的微环境，因此可能代表周围神经缺损临床修复的潜在替代方案。
A favorable microenvironment plays an important role in nerve regeneration. Extracellular matrix (ECM) derived from cultured cells or natural tissues can facilitate nerve regeneration in the presence of various microenvironmental cues, including biochemical, spatial, and biomechanical factors. This study, through proteomics and three-dimensional image analysis, determines that the components and spatial organization of the ECM secreted by bone marrow mesenchymal cells (BMSCs) are more similar to acellular nerves than those of the ECMs derived from Schwann cells (SCs), skin-derived precursor Schwann cells (SKP–SCs), or fibroblasts (FBs). ECM-modified nerve grafts (ECM-NGs) are engineered by co-cultivating BMSCs, SCs, FBs, SKP-SCs with well-designed nerve grafts used to bridge nerve defects. BMSC-ECM-NGs exhibit the most promising nerve repair properties based on the histology, neurophysiology, and behavioral analyses. The regeneration microenvironment formed by the ECM-NGs is also characterized by proteomics, and the advantages of BMSC-ECM-NGs are evidenced by the enhanced expression of factors related to neural regeneration and reduced immune response. Together, these findings indicate that BMSC-derived ECMs create a more superior microenvironment for nerve regeneration than that by the other ECMs and may, therefore, represent a potential alternative for the clinical repair of peripheral nerve defects.