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).