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To investigate whether Schwann cells could be involved in the disease pathogenesis, we developed a tissue\u2010engineered three\u2010dimensional (3D)\u00a0in 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<jats:sup>G93A<\/jats:sup> 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<jats:sup>WT<\/jats:sup> 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\u2010derived Schwann cells isolated from SOD1<jats:sup>G93A<\/jats:sup> 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.<\/jats:p>","DOI":"10.1002\/bit.28083","type":"journal-article","created":{"date-parts":[[2022,3,15]],"date-time":"2022-03-15T05:26:09Z","timestamp":1647321969000},"page":"1938-1948","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Tissue\u2010engineered in vitro modeling of the impact of Schwann cells in amyotrophic lateral sclerosis"],"prefix":"10.1002","volume":"119","author":[{"given":"Aur\u00e9lie","family":"Louit","sequence":"first","affiliation":[{"name":"LOEX Centre de recherche du CHU de Qu\u00e9bec\u2010Universit\u00e9 Laval Qu\u00e9bec City Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie\u2010Jos\u00e9e","family":"Beaudet","sequence":"additional","affiliation":[{"name":"LOEX Centre de recherche du CHU de 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