We are currently in an age where some of the most diabolical diseases are being cured and where that thing called "getting old," the enemy of many, is being forcefully pushed back. Paralysis due to spinal cord injury (SCI), causing one to live a life with few opportunities while requiring constant care, is arguably one of the greatest challenges medicine faces. Though I would certainly never disregard the challenges facing therapies in, for example, cancer, therapy for the paralyzed, with the aim of a complete function return, requires the introduction of living cells into the patient. While the pharmaceuticals given to patients with other types of diseases will affect only a specific path or several pathways, living cells can potentially affect things in a thousand different ways, often in a brand new way with each case. The enormously complex systems of living cells are far beyond our comprehension as of yet and, as such, we cannot possibly predict what will occur every time we place a mass of cells into another mass of living cells. This is especially true when that second mass is the most unknown as it gets, or as we like to call, human.
This past October at Loyola's Neuroscience Seminar, Dr. Hui Ye gave a lecture on his research on stem cells relating to SCI. He and his colleagues at the University of Toronto were studying the hypothesis that oligodendrocytes could be transplanted into a region of spinal cord injury and would promote in vivo remyelination and restoration of axon conductance. This could become a new, novel type of rehabilitation therapy for individuals suffering from paralysis due to spinal cord injury, with benefits ranging from slight muscle control or feeling to near complete and normal usage of muscles. Experimentally, Ye's group focally damaged a point along the spinal cords of mice in order to recreate the damage commonly seen in humans. Injury, as seen here, causes a crushing of the axons, which leads to demyelination. Once the myelin has been removed by the immune system's cells 'cleaning' up of the area, ion channels begin to spread out uniformly along the axon. One of the primary reasons myelination is important is its segregation of different types of ion channels along the axon, creating optimal and reliable conduction speeds along the axon. The uniform arrangement of ion channels causes extremely poor conduction along the axons, disrupting communication between the brain and muscles in the peripheral nervous system.
After injuring the mice' spinal cords, Ye's group injected differing concentrations of oligodendrocytes into the injured area. Oligodendrocytes are the cells that send out 'tendrils' to axons in the central nervous system, which then wrap around and ensheathe them with myelin. In several trials, they found that the oligodendrocytes had remyelinated some of the injured spinal cord axons and almost completely restored the non-uniform arrangement of ion channels along the axon. Further, the axon conductance speeds increased and the neurons even began to communicate with downstream neurons. However, much remains to be solved: some trials yield no results of remyelination; the factors that promote oligodendrocytes living in the transplanted environment are unknown; and working out a similar procedure to conduct on human SCI patients is extremely complex. Here we face that dilemma when working with other living things: you never know how a self-replicating, complex bundle of molecules is going to act.
Kelly Fitzgerald writes about a related and newly released study in her article "Revolutionary Stem Cell Treatment Repairs Spinal Cord Injuries in Paralyzed Dogs" on Medical News Today. Researchers at Cambridge successfully transplanted olfactory ensheathing cells (OEC), cells that support axonal growth between the nose and the brain, into dogs with hind legs paralyzed due to SCI. As a control in this double blind study, they injected just the liquids bathing OECs into a separate group of paralyzed dogs. Over the months following the transplant, the dogs injected with OECs regained much of their prior motor abilities, as their hind legs began to move with coordination between the front legs. Though new communication was found where damage had disrupted it, Fitzgerald suggests that "the new nerve connections causing this
recovery were happening over short distances within the spinal cord and
not among long distances needing the brain to connect with the spinal
cord." However, this being one of the first double blinded and randomized experiments to study the effectiveness of transplanted cells, its success is groundbreaking. Fitzgerald goes on to quote Dr. Rob Buckle, Head of Regenerative Medicine at Cambridge, "This proof of concept study... is tremendously important and an
excellent basis for further research in an area where options for
treatment are extremely limited." And even more hopeful, Fitzgerald states that a phase 1 human trial has determined that the procedure is safe for humans.
Though we are far, far away from completely curing SCIs and providing the paralyzed with a regain of function, research is definitely showing that we've made quite a bit of progress. It seems that we have a far better understanding of not only how the injury affects the spinal cord neurons, but also of the general approach required to heal the injuries. The extraordinarily complex living systems involved in both SCIs and potential cellular cures are slowly becoming understood, contributing to both the potential of SCI rehabilitation and our understanding of how living systems interact with one another as a whole.
Sources
[1] Dr. Hui Ye Lecture at Loyola's Neuroscience Seminar
[2]http://www.medicalnewstoday.com/articles/252982.php
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