Myelin regrown in multiple sclerosis models

Ordinary skin cells have been directly converted into the myelinating cells destroyed in multiple sclerosis, according to two new papers in Nature Biotechnology.

Using a process they call “cellular reprogramming,” researchers at Stanford University School of Medicine and Case Western Reserve School of Medicine, in two very similar papers, described how they turned the fibroblasts into what appear to be oligodendrocyte precursor cells, in mice. Oligodendrocytes produce myelin, the fatty insulation necessary to allow nerve signal conduction. It is caused by an autoimmune reaction attacking the oligodendrocytes.

” We propose direct lineage reprogramming as a viable alternative approach for the generation of OPCs for use in disease modeling and regenerative medicine,” the Stanford team stated in their paper.

In multiple sclerosis, the destruction of oligodendrocytes and myelin results in symptoms such as loss of balance, problems moving arms and legs, loss of coordination and weakness, according to the National Institues of Health. Other problems include loss of bladder control, impaired vision, depression, and memory loss.

To fix these problems, not only must the autoimmune reaction be brought under control, but the myelin must be repaired. That implies producing new oligodendrocytes. Hence, the OPCs, which researchers think could become effective sources of the olgodendrocytes when transplanted. (Transplantion of fully mature cells doesn’t seem to work in such studies; the cells seem to need to complete the last step of maturation in their new enviroment to wire into the nervous system.)

But until very recently, making OPCs has extremely difficult. In February, a team led by University of Rochester scientists created oligodendrocytes from induced pluripotent stem cells, which themselves were derived from fibroblasts. These cells were transplanted into animal models of multiple sclerosis, where they produced myelin.

The University of Rochester team’s approach added IPS cells to other sources of oligodendrocytes, including stem cells committed to producing neural lineage-committed stem cells and embryonic stem cells. However, all of these sources require the cells to be taken through intermediate steps to get to the desired cell. By contrast, direct conversion offers a less complicated route, and avoids the troublesome pluripotent stage, in which cells are prone to form tumors.

Ian Wilmut discusses direct cell conversion

If the Case Western or Stanford technology turns out to be useful for MS patients, it will help confirm the prediction of Ian Wilmut not long ago that direct conversion would become feasible and ultimately supplant the use of stem cells. The Case Western team spelled out this vision in their paper:

“With further optimization, this approach could provide a source of functional OPCs that will complement, and possibly obviate, the use of pluripotent stem cells and fetal cells in cell-based remyelinating therapies,” the Case Western paper stated.

The induced oligodendrocyte precursor cells, or iOPCs, just produce oligodendrocytes, the paper said, while neural stem cells and induced neural stem cells are inefficient in producing them, and they produce other unwanted cells such as neurons and astrocytes.

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