Extracellular matrix signatures of decellularized multiple sclerosis brain tissue
Extracellular matrix signatures of decellularized multiple sclerosis brain tissue
Multiple sclerosis (MS) is a chronic, progressive inflammatory disease of the central nervous system, characterized by local inflammation, loss of myelin, and neurodegeneration. When myelin degenerates, lesions form in both the white and the grey matter, while progression is additionally driven by more diffuse pathology. Stimulating myelin regeneration and preventing diffuse damage are important therapeutic targets.
In this thesis of Jody de Jong, the focus lies on the extracellular matrix (ECM), the supportive tissue located between cells and how it is affected in MS. The ECM is a dynamic network that plays an important role in repair after tissue damage. We developed a method to remove cells from thin slices of human brain tissue, while the supportive tissue remained. Using discovery proteomics, we identified the present ECM proteins. To study the direct effect of the ECM on brain cells, we separately reintroduced them to this ECM.
In the grey matter, we observed that ECM protein composition in the supportive tissue of people with MS already changes without signs of myelin degeneration. These early changes affect microglia and may contribute to diffuse pathology. In the white matter, changes in the supportive tissue occur only in lesions. Strikingly, the ECM in lesions does not directly prevent maturation of progenitor cells into myelin-forming cells. This suggests that the supportive tissue indirectly influences myelin regeneration.
These findings highlight the importance of region-specific ECM changes in MS pathology. Further research into the role of ECM may provide new therapeutic targets for treatment strategies that slow down or halt MS progression.