Tissue-engineered in vitro modeling of the impact of Schwann cells in amyotrophic lateral sclerosis.

TitleTissue-engineered in vitro modeling of the impact of Schwann cells in amyotrophic lateral sclerosis.
Publication TypeJournal Article
Year of Publication2022
AuthorsLouit, A, Beaudet, M-J, Gros-Louis, F, Berthod, F
JournalBiotechnol Bioeng
Date Published2022 Mar 15
ISSN1097-0290
Abstract

Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disease affecting upper and lower motor neurons (MNs). To investigate whether Schwann cells could be involved in the disease pathogenesis, we developed a tissue-engineered three-dimensional (3D) in vitro model that combined MNs cocultured with astrocytes and microglia seeded on top of a collagen sponge populated with epineurium fibroblasts to enable 3D axonal migration. C2C12 myoblasts were seeded underneath the sponge in the presence or absence of Schwann cells. To reproduce an ALS cellular microenvironment, MNs, astrocytes, and microglia were extracted from SOD1 mice recapitulating many aspects of the human disease. This 3D ALS in vitro model was compared with a 3D control made of cells isolated from SOD1 mice. We showed that normal Schwann cells strongly enhanced MN axonal migration in the 3D control model but had no effect in the ALS model. However, ALS-derived Schwann cells isolated from SOD1 mice failed to significantly improve axonal migration in both models. These results suggest that a cell therapy using healthy Schwann cells may not be effective in promoting axonal regeneration in ALS. In addition, this 3D ALS model could be used to study the impact of other cell types on ALS by various combinations of normal and diseased cells.

DOI10.1002/bit.28083
Alternate JournalBiotechnol Bioeng
PubMed ID35289393
Grant List / / ALS Society of Canada /
/ / Fondation Brain Canada /