Muscle weakness, dizziness, difficulty concentrating, and even visual disturbances—multiple sclerosis (MS) is a progressive disease rooted in nerve fiber damage. With no treatment available to halt the disease in its tracks, many hopes are turning to stem cell transplants.
Because under pathological attacks from the immune system, it is not only the myelin sheaths (a protein) that allow nerve information to circulate that are destroyed, but also the cells responsible for their renewal, the oligodendrocytes. What if instead of replacing myelin, stem cell transplantation allowed these oligodendrocytes to be renewed? This is the feat that researchers have achieved on mice and human stem cells, in results published in the journal Brain.
In multiple sclerosis, the challenge is remyelination
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“ Stem cell transplantation (in mice) increased the number of myelin-producing cells in the damaged area by more than 30 times", rejoices Stefano Pluchino, neuroscientist at the University of Cambridge, who led this new work. Transplanting neural stem cells (which can mature into different types of neurons and brain cells) into humans is possible and can be done without harming the patient, demonstrated two clinical trials published in 2023 in Nature Medicine And Cell Stem Cell.
Secondary analyses had even suggested an improvement in the levels of anti-inflammatory and neuroprotective molecules in the cerebrospinal fluid surrounding the brain, as well as a slowdown in brain atrophy. But in animal models, which allow for in-depth examination of lesions, most of the transplanted cells remain undifferentiated and therefore unable to contribute to the remyelination (the reconstitution of the myelin sheath) of nerve fibers. Moreover, the use of a single donor, namely cell lines derived from human fetuses, required the use of an immunosuppressant to prevent rejection.
A 30-fold increase in the number of myelin-producing cells
In this new work, the scientists used induced neural stem cells (iNSCs), that is, cells created in the laboratory from cells taken from the subject so that they are compatible. We focused on developing these iNSCs and elucidating the mechanisms to enhance remyelination within chronic lesions in mouse models. (mouse, editor's note) of MS", summarizes Stefano Pluchino. To do this, the scientists inject the CSn directly into the lesions in their spinal cord.
It was a success. With both mouse and human stem cells, the mouse myelin sheaths were repaired, “ both by stimulating the body's repair efforts and by directly becoming myelin-producing cells" , and the number of myelin-producing cells had increased 30-fold. The stem cells were already partially on their way to becoming myelin-producing cells, and we believe the environment of the damaged area helped them finish the job and transform into healthy oligodendrocytes.", interprets Stefano Pluchino.
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“ We were particularly excited by the effectiveness of stem cells in a situation where the lesions were old, and by the fact that human stem cells could survive longer and make myelin.", adds the researcher. Within the collaborative research project RESTORE, bringing together European and American scientists working to treat MS, the team is already working to apply these results in a clinical trial. " We are cautiously optimistic that this work will provide critical insights into the future of regenerative medicine for this devastating disease." hopes Stefano Pluchino.
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