Neural Regeneration Research ›› 2021, Vol. 16 ›› Issue (1): 186-191.doi: 10.4103/1673-5374.289436

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Laminin-coated multifilament entubulation, combined with Schwann cells and glial cell line-derived neurotrophic factor, promotes unidirectional axonal regeneration in a rat model of thoracic spinal cord hemisection

Ling-Xiao Deng1, 2, Nai-Kui Liu1, 2, Ryan Ning Wen3, Shuang-Ni Yang1, 2, Xuejun Wen4, Xiao-Ming Xu1, 2, *   

  1. 1 Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA;   2 Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, IN, USA;  3 Maggie L. Walker Governor’s School, Richmond, VA, USA;  4 Institute for Engineering and Medicine, Department of Chemical and Life Science Engineering, Virginia Commonwealth University, Richmond, VA, USA
  • Online:2021-01-15 Published:2020-11-26
  • Contact: Xiao-Ming Xu, PhD, xu26@iupui.edu.
  • Supported by:
    Research in the Xu laboratory is supported by NIH 1R01 100531, 1R01 NS103481, Merit Review Award I01 BX002356, I01 BX003705, I01 RX002687 from the U.S. Department of Veterans Affairs, and Mari Hulman George Endowment Funds.

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Abstract: Biomaterial bridging provides physical substrates to guide axonal growth across the lesion. To achieve efficient directional guidance, combinatory strategies using permissive matrix, cells and trophic factors are necessary. In the present study, we evaluated permissive effect of poly (acrylonitrile-co-vinyl chloride) guidance channels filled by different densities of laminin-precoated unidirectional polypropylene filaments combined with Schwann cells, and glial cell line-derived neurotrophic factor for axonal regeneration through a T10 hemisected spinal cord gap in adult rats. We found that channels with filaments significantly reduced the lesion cavity, astrocytic gliosis, and inflammatory responses at the graft-host boundaries. The laminin coated low density filament provided the most favorable directional guidance for axonal regeneration which was enhanced by co-grafting of Schwann cells and glial cell line-derived neurotrophic factor. These results demonstrate that the combinatorial strategy of filament-filled guiding scaffold, adhesive molecular laminin, Schwann cells, and glial cell line-derived neurotrophic factor, provides optimal topographical cues in stimulating directional axonal regeneration following spinal cord injury. This study was approved by Indiana University Institutional Animal Care and Use Committees (IACUC #:11011) on October 29, 2015.

Key words: axonal regeneration, extracellular molecule, filament density, hemisection, laminin, neurotrophic factor, Schwann cell, spinal cord injury, thoracic, transplantation