Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.28.358705v1?rss=1 Authors: Tepavcevic, V., Dufayet-Chaffaud, G., Aigrot, M.-S., Gillet-Legrand, B., Tada, S., Izagirre, L., Cartier, N., Lubetzki, C. Abstract: Despite extensive progress in immunotherapies that reduce inflammation and relapse rate in patients with multiple sclerosis (MS), preventing disability progression associated with cumulative neuronal/axonal loss remains an unmet therapeutic need. Complementary approaches have established that remyelination prevents degeneration of demyelinated axons. While several pro-remyelinating molecules are undergoing preclinical/early clinical testing, targeting these to disseminated MS plaques is a challenge. In this context, we hypothesized that monocyte (blood) -derived macrophages may be used to efficiently deliver repair-promoting molecules to demyelinating lesions. Here, we used transplantation of genetically-modified hematopoietic stem cells (HSCs) to obtain circulating monocytes that overexpress Semaphorin 3F, a pro-remyelinating molecule. We show that Semaphorin 3F-expressing macrophages quickly infiltrate demyelinating spinal cord lesions, which increases oligodendrocyte progenitor cell recruitment and accelerates myelin repair. Our results provide a proof-of-concept that monocyte-derived macrophages could be used to deliver pro-remyelinating agents "at the right time and place", suggesting novel means for remyelinating therapies in patients with MS. Copy rights belong to original authors. Visit the link for more info