Transplantation of Cerebral Dopamine Neurotrophic Factor Transducted BMSCs in Contusion Spinal Cord Injury of Rats: Promotion of Nerve Regeneration by Alleviating Neuroinflammation

Abstract

Traumatic spinal cord injury (SCI) causes neuron death and axonal damage resulting in functional motor and sensory loss, showing limited regeneration because of adverse microenvironment such as neuroinflammation and glial scarring. Currently, there is no effective therapy to treat SCI in clinical practice. Bone marrow-derived mesenchymal stem cells (BMSCs) are candidates for cell therapies but its effect is limited by neuroinflammation and adverse microenvironment in the injured spinal cord. In this study, we developed transgenic BMSCs overexpressing cerebral dopamine neurotrophic factor (CDNF), a secretory neurotrophic factor that showed potent effects on neuron protection, anti-inflammation, and sciatic nerve regeneration in previous studies. Our results showed that the transplantation of CDNF-BMSCs suppressed neuroinflammation and decreased the production of proinflammatory cytokines after SCI, resulting in the promotion of locomotor function and nerve regeneration of the injured spinal cord. This study presents a novel promising strategy for the treatment of spinal cord injury.

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Acknowledgments

The authors are grateful to Prof. Tang DQ, Wang XL, Research Center for Cell Therapy, Qilu Hospital of Shandong University, and Prof. Chen ZY, Department of Neurobiology, Shandong University, for their kind advice and help with this research. The study was supported by the grant from Ph.D. Programs Foundation of Ministry of Education of China (20110131120079) and Natural Science Foundation of Shandong Province, China (ZR2013HM095).

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The authors declare that there is no conflict of interests regarding the publication of this paper.

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Correspondence to Lin Nie.

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Hua Zhao and Lei Cheng contributed equally to this study.

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Zhao, H., Cheng, L., Du, X. et al. Transplantation of Cerebral Dopamine Neurotrophic Factor Transducted BMSCs in Contusion Spinal Cord Injury of Rats: Promotion of Nerve Regeneration by Alleviating Neuroinflammation. Mol Neurobiol 53, 187–199 (2016). https://doi.org/10.1007/s12035-014-9000-6

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Keywords

  • Spinal cord injury
  • Cell therapy
  • Bone marrow-derived mesenchymal stem cells
  • Cerebral dopamine neurotrophic factor
  • Nerve regeneration
  • Neuroinflammation