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Origin of cells associated with nerve repair discovered

Cambridge Neuroscientists 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.

Article by the University Press Office.

During subsequent correspondence with Cambridge Neuroscience Clare additionally highlighted the importance of funding blue-skies research, and the potential translational applications which may arise from such projects, as was the case here:

"I think our discovery is a good example of how "blue-skies" research (i.e., research that aims to discover how the world works, without any obvious immediate applications to medicine or technology) can yield totally unexpected outcomes, with potentially very significant applications that could not possibly have been predicted in advance.

Of course, we're a long way from knowing whether or not our research will indeed improve cell transplantation therapy for spinal cord repair. If it does, I think it's important to recognise that this research came about because of an accidental discovery made in the course of a project with very different aims. The longterm impact of the original project, therefore, could not possibly have been
predicted in advance.

The Wellcome Trust funded a pilot project in my lab to look at neural crest cell contributions to the developing olfactory system for a completely different reason - we were looking at the embryonic origin of nerve cells that make hormones important for reproduction. We could not possibly have predicted that we would end up discovering that OECs are derived from neural crest cells, or that our original research project might end up having an impact on cell transplantation therapy for spinal cord repair".

Research Article (open access), here.


Posted on 17/11/2010

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