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Stem Cells Transformed Into Myelinating Cells in Mice

Researchers from Case Western Reserve University School of Medicine discovered a way to differentiate mice stem cells into cells that give rise to protective myelin coating. The finding is an important step towards new treatments for cerebral palsy, multiple sclerosis and other conditions associated with myelin loss. The finding was reported in Nature Methods, on Sept. 25.

Myelin covers nerve axons and serves for protecting them and providing insulation needed for transmission of signals along nerves. When myelin is lost, nerves get damaged and nerve signals are not carried effectively, which results in symptoms such as loss of coordination etc.

Though it has been long known that pluripotent stem cells can give rise to myeninating cells, or oligodendrocyte progenitor cells (OPCs), the previous efforts of guiding stem cell differentiation into these cells resulted in production of mixed cell cultures. That made these cells unsuitable for research or treatment.

The researchers set a goal to produce myelinating cells that could restore the damaged myelin. They used epiblast stem cells that are pluripotent, i.e. able to give rise to different specialized cells, and developed methods that would ensure differentiation of these cells into OPCs. The team was able to repeat the same cell differentiation path that occurs during embryonic development. All the process of producing OPCs took 10 days.

At the first stage, with the use of special molecules, stem cells in petri dish were converted into the most primitive cells found in the nervous system. Then these cells were organized into neural rosettes. At the next stage neural rosettes were treated with specific signaling proteins that are important for production of OPCs in the spinal cord development process. After this 10-day period was finished, the scientists could maintain growth of the received OPCs on the special substrate with addition of growth factors crucial for OPS development. This resulted in more than a trillion OPCs cells produced. After that, the researchers treated oligodendrocyte progenitor cells with thyroid hormone that is responsible for transformation of OPCs into olygodendrocytes and received the latter within four days.

When the researchers used OPCs, either in lab or in the mice models, the OPCs succeccfully developed into oligodendrocytes and replaced damaged myelin with normal one within a few days, proving potential OPCs use in stem cell therapy of multiple sclerosis and other conditions associated with demyelination.

The researchers believe the same process may be used to manipulate patient’s own stem cells to produce OPCs that would restore damaged myelin and reverse the disease.