Scientists skip stem cell stage to make myelin in mice

Skin cells have been directly converted into the types of cells destroyed in patients with myelin disorders such as multiple sclerosis and cerebral palsy in a pair of studies on mice.

Dr Paul Tesar of Case Western Reserve School of Medicine in the US, a senior author of the study, said of the technique: 'It's "cellular alchemy". We are taking a readily accessible and abundant cell and completely switching its identity to become a highly valuable cell for therapy'.

Many brain and nerve cells need to be insulated in myelin to function correctly. If the coating of myelin is lost or damaged, nerve signals cannot travel as quickly or as far as they should and so diseases which attack myelin can lead to cognitive, motor and sensory problems.

In the first study, researchers at Stanford University made mouse skin cells express three transcription factors which induced the cells to convert into oligodendrocyte precursor cells (OPCs). These cells were capable of regenerating the myelin coating around nerve cells upon transplantation in mice. In the second study from Case Western Reserve, sets of either three or eight transcription factors were used to generate functional OPCs.

This is not the first time functional OPCs have been generated from other cell types. But previous studies have used embryonic stem cells or skin cells which have first been transformed into induced pluripotent stem cells before conversion to OPCs (reported in BioNews 692).

There are, however, limitations when using these approaches, not least in often disappointing yields of cells at the end of the process. 'The myelin repair field has been hampered by an inability to rapidly generate safe and effective sources of myelin-producing cells', said Professor Robert Miller from Case
Western Reserve. He added that the new technique 'may overcome all of these issues'.

Dr Nan Yang, lead author of the Stanford study, explained that 'by using the patient's own skin cells, we should be able to generate transplantable OPCs that are genetically identical to the patient's natural OPCs. This allows us to avoid the problem of immune rejection, which is a major complication in transplantation medicine'.

Since mouse cells were used in these studies, the next step would be to confirm these approaches in human cells. If successful, it would not be the first time that human skin cells have been directly converted into brain cells (see BioNews 658).