Viral delivery of L1CAM promotes axonal extensions by embryonic cerebral grafts in mouse brain

IR (HANDLE) Open Access
  • Tsuchimochi, Ryosuke
    Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University; Department of Neurosurgery, Graduate School of Medical Sciences, Kyushu University
  • Yamagami, Keitaro
    Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University; Department of Neurosurgery, Graduate School of Medical Sciences, Kyushu University
  • Kubo, Naoko
    Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University
  • Amimoto, Naoya
    Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University
  • Raudzus, Fabian
    Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University
  • Samata, Bumpei
    Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University
  • Kikuchi, Tetsuhiro
    Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University
  • Doi, Daisuke
    Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University
  • Yoshimoto, Koji
    Department of Neurosurgery, Graduate School of Medical Sciences, Kyushu University
  • Mihara, Aya
    Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University
  • Takahashi, Jun
    Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University; Department of Neurosurgery, Kyoto University Graduate School of Medicine

Description

Cell replacement therapy is expected as a new and more radical treatment against brain damage. We previously reported that transplanted human cerebral organoids extend their axons along the corticospinal tract in rodent brains. The axons reached the spinal cord but were still sparse. Therefore, this study optimized the host brain environment by the adeno-associated virus (AAV)-mediated expression of axon guidance proteins in mouse brain. Among netrin-1, SEMA3, and L1CAM, only L1CAM significantly promoted the axonal extension of mouse embryonic brain tissue-derived grafts. L1CAM was also expressed by donor neurons, and this promotion was exerted in a haptotactic manner by their homophilic binding. Primary cortical neurons cocultured on L1CAM-expressing HEK-293 cells supported this mechanism. These results suggest that optimizing the host environment by the AAV-mediated expression of axon guidance molecules enhances the effect of cell replacement therapy.

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Details 詳細情報について

  • CRID
    1050858751945792384
  • ISSN
    22136711
  • HANDLE
    2433/281598
  • Text Lang
    en
  • Article Type
    journal article
  • Data Source
    • IRDB

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