Ependymal cells are a largely understudied barrier cell type in the brain that provide a wall between brain tissue and brain fluid (cerebral spinal fluid, CSF), playing an important role in regulating fluid balance. These cells become dysfunctional in many brain diseases and this dysfunction contributes to neurodegeneration that occurs across many brain conditions. Specifically, in diseases like Multiple Sclerosis (MS), where ependymal cells are badly damaged, they can no longer perform basic functions such as supporting fluid flow, which is necessary to maintain healthy brains. We have discovered that ependymal cells are particularly sensitive to immune cell damage, and think that this inflammatory damage is causing ependymal cell dysfunction in MS. To test this hypothesis, we have created a culture system to assess how ependymal cells become damaged from inflammation in MS.
We will assess the function of ependymal cells following MS inflammatory insult, and identify specific inflammatory molecules that are responsible for dysfunction. Firstly, we will derive human ependymal cells from stem cells, and culture these cells for several days to ensure they become mature and functional. Then we will apply CSF from MS and control donors to learn how factors from diseased brains affect ependymal cell health and function. We will assess how the cells look, whether they are damaged and whether fluid movement is affected.
This research will have profound implications for Canadians, where currently the mechanisms underlying MS progression is largely unknown, and therefor hard to target, therapeutically. By understanding all aspects of MS disease, and how different cell types in the brain are affected by inflammation, we will uncover uncharacterized mechanisms of disease progression that can be targeted to better treat MS patients.