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

First Author  Tsuchimochi R Year  2023
Journal  Stem Cell Reports Volume  18
Issue  4 Pages  899-914
PubMed ID  36963389 Mgi Jnum  J:335515
Mgi Id  MGI:7470348 Doi  10.1016/j.stemcr.2023.02.012
Citation  Tsuchimochi R, et al. (2023) Viral delivery of L1CAM promotes axonal extensions by embryonic cerebral grafts in mouse brain. Stem Cell Reports 18(4):899-914
abstractText  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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