Neural Regeneration Research ›› 2021, Vol. 16 ›› Issue (11): 2276-2283.doi: 10.4103/1673-5374.310696

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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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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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