中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2021, Vol. 16 ›› Issue (11): 2276-2283.doi: 10.4103/1673-5374.310696

• 原著:脊髓损伤修复保护与再生 • 上一篇    下一篇

去细胞化视神经功能支架移植促进大鼠损伤脊髓轴突定向再生和髓鞘再生

  

  • 出版日期:2021-11-15 发布日期:2021-04-13
  • 基金资助:

    国家重点科研计划想项目（2017YFA0104704）；中国科协青年精英科学家资助计划项目（2018QNRC001）；中央高校基本科研业务费专项资金（18ykpy38）；国家科学基金项目（81971157，81891003）

Decellularized optic nerve functional scaffold transplant facilitates directional axon regeneration and remyelination in the injured white matter of the rat spinal cord

Yu-Rong Bai, Bi-Qin Lai, Wei-Tao Han, Jia-Hui Sun, Ge Li, Ying Ding, Xiang Zeng, Yuan-Huan Ma, Yuan-Shan Zeng   

  1. 1Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou, Guangdong Province, China; 2Department of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong Province, China; 3Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu Province, China; 4Institute of Spinal Cord Injury, Sun Yat-sen University, Guangzhou, Guangdong Province, China; 5Guangdong Provincial Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong Province, China
  • Online:2021-11-15 Published:2021-04-13
  • Contact: Bi-Qin Lai, MD, laibiqin@126.com; Yuan-Shan Zeng, MD, zengysh@mail.sysu.edu.cn.
  • Supported by:
    This work was supported by grants from the National Key R&D Program of China, No. 2017YFA0104704 (to BQL); the Young Elite Scientist Sponsorship Program (YESS) by China Association for Science and Technology (CAST), No. 2018QNRC001 (to BQL); the Fundamental Research Funds for the Central Universities, China, No. 18ykpy38 (to BQL); and the National Natural Science Foundation of China, Nos. 81971157 (to BQL), 81891003 (to YSZ).

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摘要：

损伤部位轴突再生和髓鞘再生是最常见的脊髓损伤修复方法，但实施上仍然十分困难。作者既往研究发现，去细胞猪视神经更接近于胚胎猪视神经的细胞外基质成份，可促进背根神经节神经突起直行生长，但是这种材料在体内能否促进受损伤脊髓再生轴突直行生长及其重建髓鞘结构，还未见研究报道。在此次实验中，利用去细胞猪视神经负载过表达神经营养素3的许旺细胞构建了一种同时具有促进再生轴突直行生长和再髓鞘化的功能支架移植物。（1）体外实验中，与胶原海绵相比，去细胞猪视神经存在均匀分布的直行通道，其3通道壁上有微米级的小孔，其空间微拓扑结构和细胞外基质等特性，更有利于种植在其中的过表达神经营养素3的许旺细胞粘附、存活和迁移，并能促进背根神经节神经突的定向生长，并显示出强大的髓鞘再生潜力；（2）在大鼠T10脊髓缺损模型中，移植含有过表达神经营养素3的许旺细胞去细胞猪视神经功能支架移植物进行治疗。4周后，大鼠损伤脊髓再生轴突可直行生长，且损伤/移植区域髓鞘也会恢复其结构，同时可减弱炎症细胞和硫酸软骨素蛋白聚糖的表达；（3）结果表明去细胞猪视神经负载过表达神经营养素3的许旺细胞构建功能支架可促进损伤脊髓轴突的定向再生和髓鞘再生。实验于2019年2月28日经中山大学动物伦理委员会批准（批准号SYSU-IACUC-2019-B034）。

https://orcid.org/0000-0003-1978-3466 (Bi-Qin Lai); https://orcid.org/0000-0003-3804-5792 (Yuan-Shan Zeng)

关键词:

脱细胞化, 视神经, 许旺细胞, 神经营养素3, 功能支架, 轴突再生, 髓鞘再生, 白质损伤, 定向再生, 组织工程, 微环境

Abstract: Axon regeneration and remyelination of the damaged region is the most common repair strategy for spinal cord injury. However, achieving good outcome remains difficult. Our previous study showed that porcine decellularized optic nerve better mimics the extracellular matrix of the embryonic porcine optic nerve and promotes the directional growth of dorsal root ganglion neurites. However, it has not been reported whether this material promotes axonal regeneration in vivo. In the present study, a porcine decellularized optic nerve was seeded with neurotrophin-3-overexpressing Schwann cells. This functional scaffold promoted the directional growth and remyelination of regenerating axons. In vitro, the porcine decellularized optic nerve contained many straight, longitudinal channels with a uniform distribution, and microscopic pores were present in the channel wall. The spatial micro topological structure and extracellular matrix were conducive to the adhesion, survival and migration of neural stem cells. The scaffold promoted the directional growth of dorsal root ganglion neurites, and showed strong potential for myelin regeneration. Furthermore, we transplanted the porcine decellularized optic nerve containing neurotrophin-3-overexpressing Schwann cells in a rat model of T10 spinal cord defect in vivo. Four weeks later, the regenerating axons grew straight, the myelin sheath in the injured/transplanted area recovered its structure, and simultaneously, the number of inflammatory cells and the expression of chondroitin sulfate proteoglycans were reduced. Together, these findings suggest that porcine decellularized optic nerve loaded with Schwann cells overexpressing neurotrophin-3 promotes the directional growth of regenerating spinal cord axons as well as myelin regeneration. All procedures involving animals were conducted in accordance with the ethical standards of the Institutional Animal Care and Use Committee of Sun Yat-sen University (approval No. SYSU-IACUC-2019-B034) on February 28, 2019.

Key words: axonal regeneration, decellularized optic nerve, directional regeneration, functional scaffold, microenvironment, neurotrophin-3, optic nerve, remyelination, Schwann cells, tissue engineering, white matter injury

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