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一种蛋白质复合神经支架调节星形胶质细胞迁移和转录组特征。

A Protein Composite Neural Scaffold Modulates Astrocyte Migration and Transcriptome Profile.

机构信息

Department of Biological Sciences, Wichita State University, 1845 Fairmount Street, Wichita, KS, 67260, USA.

KSU Bioinformatics Center, Division of Biology, Kansas State University, Manhattan, KS, 66506, USA.

出版信息

Macromol Biosci. 2022 Apr;22(4):e2100406. doi: 10.1002/mabi.202100406. Epub 2022 Jan 18.

Abstract

Bioscaffold implantation is a promising approach to facilitate the repair and regeneration of wounded neural tissue after injury to the spinal cord or peripheral nerves. However, such bioscaffold grafts currently result in only limited functional recovery. The generation of a neural scaffold using a combination of collagen and glutenin is reported. The conduit material and mechanical properties, as well as its effect on astrocyte behavior is tested. After neural injuries, astrocytes move into the lesion and participate in the process of remodeling the micro-architecture of the wounded neural tissue. In this study, human astrocytes grown on glutenin-collagen scaffolds show higher motility and a lower proliferation rate compared with those grown on collagen scaffolds. RNA sequencing reveals that astrocytes grown on the two types of scaffolds show differentially expressed genes in Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways such as actin cytoskeleton and focal adhesion that regulate astrocyte migration on scaffolds. The gene expression of aggrecan and versican, chondroitin sulfate proteoglycans that inhibit axonal growth, is down-regulated in astrocytes grown on glutenin-collagen scaffolds. These outcomes indicate that the implantation of glutenin-collagen scaffolds may promote astrocyte function in the neural regeneration process by enhanced cell migration and reduced glial scar formation.

摘要

生物支架植入是一种有前途的方法,可以促进脊髓或周围神经损伤后受伤神经组织的修复和再生。然而,这种生物支架移植物目前仅导致有限的功能恢复。据报道,使用胶原蛋白和谷蛋白的组合来产生神经支架。测试了导管材料和机械性能及其对星形胶质细胞行为的影响。在神经损伤后,星形胶质细胞移入病变部位,并参与重塑受伤神经组织的微观结构。在这项研究中,与在胶原蛋白支架上生长的星形胶质细胞相比,在谷蛋白-胶原蛋白支架上生长的人星形胶质细胞显示出更高的迁移率和更低的增殖率。RNA 测序表明,在两种支架上生长的星形胶质细胞在京都基因与基因组百科全书(KEGG)通路中表现出差异表达的基因,例如调节星形胶质细胞在支架上迁移的肌动蛋白细胞骨架和黏着斑。在谷蛋白-胶原蛋白支架上生长的星形胶质细胞中,抑制轴突生长的软骨素硫酸蛋白聚糖 aggrecan 和 versican 的基因表达下调。这些结果表明,植入谷蛋白-胶原蛋白支架可能通过增强细胞迁移和减少神经胶质瘢痕形成来促进神经再生过程中的星形胶质细胞功能。

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