Darek Fidyka was stabbed in the back in 2010 and paralyzed from the chest down. After a year of rehab and no apparent improvement, surgeons tried a radical procedure: they extracted olfactory cells — basically, cells from the back of his nose — and transplanted them into an eight-millimeter gap at level T9 in his severed spinal cord. Now the man walks, albeit still using a frame. To dissect exactly how this procedure appears to have worked we need to understand precisely what was done during his incredible surgery, and what it is about these peculiar cells that enables neurons to reconnect.
First off, we are going to mention a few names because that is probably the best way to organize and understand the motivations for the successes that follow here. The procedure was technical tour de force that extended far beyond the few hours on the operating table. It was funded by the UK’s Nicholls Spinal Injury Foundation, a project set up by David Nicholls after his son had a shallow water diving accident. As he relates, there is no more devastating experience in life than the sight of your child lying motionless in a bed, alert, in the reality that they will never move again.
Not one to take this news lying down, Nicholls brought together Geoff Raisman, chair of neurology at University College London’s Institute of Neurology, and surgeon Pawel Tabakow from Wroclaw Medical University in Poland where the procedure was performed, to drive the spinal regeneration field ahead. After 40 years of research into regeneration, Raisman has zeroed in on a particular kind of cell, the olfactory ensheathing cell (OEC), that for many reasons is our best hope at the moment for neural regrowth. To understand what this cell can do we need to understand something about smell.
Smell is a tricky, sometimes even dangerous affair. Here you are trying to decode the most volatile, sometimes noxious, and frequently toxic molecules around. The nose also happens to be one of the best ways to gain entry into the brain, not to mention the body itself, if you happen to be a virus. For these reasons the olfactory system is one of the few, if not the only place in the brain that manages to repopulate itself with fresh neurons and support cells. Cells in the olfactory bulb where scent is processed, and also in the lining of the nose (the olfactory mucosa as it is called) where the smell receptors are found, have a comparatively short life. They are continually sloughing off, sweeping away undesirables from beyond, and getting replaced by a migratory stream of neuron newbies from the brain.
The challenge, and opportunity we might add, for the nervous system is to regrow the connections that are inevitably lost during the changing of the guard. The olfactory ensheathing cell is the guy that makes this all happen. Technically it is known as a radial glial cell, a kind of cell that provides niche nutrients and physical support for neurons. But researchers have found that this cell also shares much in common with the insulating cells that myelinate the axons of neurons, and to some extent provide a “mechanical memory” for their former targets. Raisman was the first to really understand the power of the OEC and spearhead their use for spinal regeneration where other methods based on stem cells have come up short.
One thing that Raisman discovered the hard way — as in, actual clinical trials and countless rat experiments — is that all OECs are not created equal. The OECs in the mucosa that lines the olfactory cavity do not support regeneration to the extent that OECs from the olfactory bulb do. Furthermore, another kind of cell, the olfactory fibroblast, proved to be an essential connective-tissue-forming cell that needed to be transplanted along with OECs to get full benefit.
Next page: Details of the surgery that allowed Darek Fidyka to walk again
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