1. Viral delivery of L1CAM promotes axonal extensions by embryonic cerebral grafts in mouse brain
- Author
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Ryosuke Tsuchimochi, Keitaro Yamagami, Naoko Kubo, Naoya Amimoto, Fabian Raudzus, Bumpei Samata, Tetsuhiro Kikuchi, Daisuke Doi, Koji Yoshimoto, Aya Mihara, and Jun Takahashi
- Subjects
corticospinal tract ,axon guidance molecule ,Cell Biology ,axonal extension ,gene therapy ,semaphorin ,Biochemistry ,adeno-associated virus vector ,L1CAM ,netrin-1 ,Genetics ,cerebral cortex ,cell transplantation ,Developmental Biology - Abstract
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., 遺伝子治療によるホスト脳の環境最適化が細胞移植効果を高める --ホスト脳へのL1CAMの強制発現によるマウス胎仔脳移植片の軸索伸長促進効果--. 京都大学プレスリリース. 2023-03-24., Combining cell transplantation and gene therapy to enhance axonal outgrowth in the central nervous system. 京都大学プレスリリース. 2023-04-06.
- Published
- 2023