Scientists have discovered the origin of a unique type of cell
known for its ability to support regeneration in the central
nervous system. Their findings, published this week in the journal
Proceedings of the National Academy of Sciences USA
(PNAS), raise the possibility of obtaining a more reliable
source of these cells for use in cell transplantation therapy for
spinal cord injuries.
Olfactory ensheathing cells (OECs), as the name suggests,
ensheath and protect the nerve fibres in the olfactory nerve, which
transmit olfactory (smell) information to the brain from receptor
cells sitting in the lining of the nose. Excitingly, OECs can
promote nerve repair when transplanted into the damaged spinal
cord. They can also be grown in dishes from pieces of nasal lining
but, unfortunately, in such small quantities that this may not be a
viable option for use in treatments.
Dr Clare Baker, from the Department of Physiology, Development
and Neuroscience at the University of Cambridge, lead author of the
study, said: "In theory, one should be able to purify OECs from a
patient's nose and transplant them into the damaged spinal cord to
promote nerve repair, without any fear of graft rejection.
"Unfortunately, there aren't very many OECs in the nasal lining,
and this tissue also contains other peripheral nerve fibres,
ensheathed by cells that look very similar to OECs but which are
less effective at promoting spinal cord repair. As a result, it has
thus far proven difficult to purify sufficiently large numbers of
OECs from the nasal lining for effective use in cell
transplantation therapy."
For the last 25 years, OECs have been thought to be formed by
the nasal lining itself. The new research, however, reveals a
different origin for OECs that may enable scientists in the future
to produce them in large quantities from adult stem cells.
The researchers, funded by the Wellcome Trust and the Isaac
Newton Trust, have discovered that, like all other cells
ensheathing peripheral nerve fibres, OECs are actually derived from
a group of embryonic stem cells called "neural crest cells". Neural
crest stem cells persist in adult skin and hair follicles, and
other researchers have already shown that it is possible to isolate
these stem cells and grow them in the lab.
Dr Baker said, "The next step is to work out how to turn these
stem cells into OECs. To do this, we need to investigate how this
process happens normally in the developing embryo."
Dr Baker continued, "It is important to note that it will take
many years for our research to have any impact on therapy for
people with damaged spinal cords. However, we are hopeful that our
discovery provides a fresh starting point for new research into
ways of purifying large numbers of these cells for use in
treatments."
In order to determine the origin of OECs, the scientists tagged
embryonic neural crest cells with 'green fluorescent protein'
(GFP), so that only neural crest cells and their descendants glowed
green under ultraviolet light. They did this in chicken embryos by
transplanting GFP-labelled neural crest cells into unlabelled host
embryos; they also looked at mouse embryos in which, through a
genetic trick, the only cells that expressed GFP were neural crest
cells.
They were then able to follow what happened to neural crest
cells and their descendants as the olfactory nerve developed. By
analysing thin sections of these embryos under the microscope, they
were able to see that lots of green neural crest-derived cells were
associated with the developing olfactory nerve fibres. These green
cells expressed molecular markers characteristic of OECs, and
crucially, they ensheathed bundles of the olfactory nerve fibres,
i.e., they were indeed olfactory ensheathing cells.
SOURCE