New technique maps out cellular architecture of lesions in MS

March 22, 2024
Using an advanced technique, scientists were able to reveal at the cellular level how lesions in multiple sclerosis develop. 

MS is characterized by lesions in the brain and the spinal cord. More than 1.8 million people worldwide are diagnosed with MS. In this disease, the body's own immune cells attack cells that create myelin, oligodendrocytes, which belong to the group of glial cells. Without myelin, signals between nerve cells cannot travel as fast as usual, resulting in symptoms such as reduced sensation and lack of coordination. 

The researchers at the Department of Medical Biochemistry and Biophysics, Karolinska Institute, and Stockholm University, in Sweden used a technology called in situ sequencing. This involves analyzing and identifying cells that are part of a tissue section by reading which genes are active in a particular cell. This pattern reveals how different cell types are arranged in the tissue, in this case the spinal cord, and how the cells interact with each other. To study how the lesions develop, samples were taken at different times from mice experimentally induced with symptoms that mimic MS, and from human MS patients.

The researchers simultaneously analyzed 239 genes and found that active lesions in mice were built up centrifugally in two dimensions, with immune cells in the middle and different types of glial cells around them. In the mice, it was possible to see the lesions first appeared in the spinal cord and then spread towards the brain. In samples of the spinal cord from four deceased MS patients, 260 genes were simultaneously analyzed and the cellular architecture of the lesions could be determined. The authors also found new lesions and new substructures within the lesions.

Previously, oligodendrocytes have mainly been seen as victims of immune cell attacks. Researchers said the fact that they are active in the outer regions of lesions and in the entire brain and spinal cord raises the question of whether they dampen the disease or drive it.

In the next step, the researchers want to use the same technique to analyze samples from more MS patients. Another question is what the lesions look like when patients have received different types of treatments.

The new results are presented in the journal “Cell.”

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