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Direct reprogramming of astrocytes for spinal cord injury

Friday, May 3, 2024

    Presenting Author(s)

  • Yoon Ha, MD, PhD

    Professor
    Yonsei University College of Medicine, Department of Neurosurgery
    Seoul, Republic of Korea

    • Co-Author(s)

  • HL

    Hye Yeong Lee, Ph.D

    research assistant professor
    Yonsei Uinversity College of Medicine, United States

  • HL

    Hye-Lan Lee, Ph,D

    research assistant professor
    1Spine & Spinal Cord Institute, Department of Neurosurgery, College of Medicine, Yonsei University,, United States

Introduction: Spinal cord injury is induced by trauma or compression that often leads to blocking the stimulus, and disorder to function of motor system, sensory and autonomic nervous system. The fundamental treatment of spinal cord injury is not yet developed. Generally, it has been applied that decompression therapy, drug treatment and rehabilitation for spinal cord injury. However, the treatments have shown that limited effects. Because of that reason, new treatments are in the studying including gene therapy and stem cell therapy. Among them, in vivo reprogramming is regarded as promising futuristic technology. In this study, we develop the in vivo reprogramming system for treatment of spinal cord injury by reprogramming the astrocytes to neurons

Methods: In this study, we used human astrocytes and it was directly reprogrammed by specific vectors for 6 weeks. After then reprogrammed cells were verified by immunocytochemistry. At the In vivo study, male C57BL/6 mice (postnatal 7 weeks) were randomized into four groups: Group 1= sham group, Group 2= PBS group, Group3= Ctrl vector injected group and Group4= reprogrammed group. Genetic transduction was conducted 2 weeks after spinal cord injury and subjects were observed for 6 weeks. To evaluate functional behavior, each group was examined with basso mouse scale (open field test). Also, immunohistochemistry proceed for reveal in vivo direct reprogramming and neuronal regeneration.

Results: In this research, we developed the new type of In vivo reprogramming. For check the system working, new system was transduced to astrocytes in vitro. The astrocytes were induced to neurons and GFP was positively expressed. As well as, new system induced neurons from astrocytes in spinal cord injured animals. The reprogrammed neurons improved the animal behavior.

Conclusion : From these results, we can confirm the new system works as new in vivo reprogramming system. Also they have the potential to new treatment for spinal cord injury.