Lesion stage-dependent causes for impaired remyelination in MS

• DOI: 10.1007/s00401-020-02189-9
• Publication Date: 2020-07-24T19:03:52Z
• Authors: Katharina Heß; Laura Starost; Nicholas W. Kieran; Christian Thomas; Maria C. J. Vince...; Jack Antel; Gianvito Martino; Inge Huitinga; Luke Healy; Tanja Kuhlmann
• Keywords: Remyelination; Demyelinating disease

Abstract Multiple sclerosis (MS) is the most frequent demyelinating disease and a leading cause for disability in young adults. Despite significant advances immunotherapies recent years, progression still cannot be prevented. Remyelination, meaning formation of new myelin sheaths after event, can fail MS lesions. Impaired differentiation progenitor cells into myelinating oligodendrocytes may contribute to remyelination failure and, therefore, development pharmacological approaches which promote oligodendroglial by that remyelination, represents promising treatment approach. However, this generally accepted concept has been challenged recently. To further understand mechanisms contributing MS, we combined detailed histological analyses assessing cell numbers, presence as well inflammatory environment different lesion types white matter with vitro experiments using induced-pluripotent stem (iPSC)-derived (hiOL) supernatants from polarized human microglia. Our findings suggest there are multiple reasons dependent on stage. These include lack sheath despite mature subset active lesions loss hostile tissue mixed active/inactive Therefore, conclude better vivo models mimic pathological hallmarks required successful promoting drugs.