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Human stem cell models point to glia as key players in MS
August 29, 2024
Researchers have created the largest reported collection of stem cell models from multiple sclerosis patients and used them to identify unique ways in which glial cells – integral support cells in the brain – contribute to the disease. The study is the first to report that glial cells from MS patients have intrinsic hallmarks of disease, independent from the influences of the immune system. That points to the power of stem cells for revealing new disease biology and to the need for new types of MS therapies.
MS is an autoimmune disease that occurs when the body’s immune system mistakenly attacks the protective myelin sheaths that surround the nerves in the brain and spinal cord, resulting in significant neurological disability.
Scientists from the New York Stem Cell Foundation Research Institute and Case Western Reserve University leveraged the power of NYSCF’s automation platforms to create induced pluripotent stem cells from skin biopsies of individuals with MS, resulting in the largest collection of MS patient stem cell lines to date, spanning diverse clinical subtypes. They then converted the iPSCs into glial cells – which include oligodendrocytes and astrocytes – to investigate their role in the disease.
Using single-cell gene expression profiling, the scientists found stem cell-derived glia cultures from people with primary progressive MS (a particularly severe form of the disease) contained fewer oligodendrocytes. Oligodendrocytes are responsible for producing myelin, the protective sheath around nerve fibers that is lost in MS.
The team also observed that a set of genes linked to immune and inflammatory functions were particularly active in stem cell-derived glia cultures from MS patients, matching what they see in brain samples from deceased individuals with MS. Moreover, NYSCF scientists leveraged their latest advances in artificial intelligence to detect differences in astrocytes that are not easily seen by the human eye.
Because of the autoimmune activity in MS, many current therapies target the immune system. These drugs help reduce the frequency of immune attacks, but they unfortunately fall short at preventing the neurodegeneration that drives disease progression.
The study’s findings open new possibilities for treating MS. By identifying specific glial cell behaviors that contribute to the disease, researchers can now explore potential therapies that target these cells directly. This could lead to more effective treatments that go beyond simply suppressing the immune system and offer new hope for patients.
The study was published in
Cell Stem Cell
.
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