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SCI Care: What Really Matters
SCI Care: What Really Matters
Stem cell therapies for spinal cord injury - Where are we now and where are we going?
Dr. Michael G. Fehlings
discusses the future of stem cell therapies for spinal cord injury
with Intissar Mohcine & Asma Belarbi, high-school students from the Netherlands.
Key points:
1) Stem cells are a promising therapeutic approach to repair the damaged spinal cord following injury.
2) Preclinical studies have shown exciting improvements in spinal cord structure and motor function.
3) A number of issues still need to be resolved before stem cell therapy can be successfully utilized in the clinical setting.
The opinions of our host and guests are their own; ISCoS does not endorse any individual viewpoints, given products or companies.
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The SCI Care: What Really Matters podcast aims to provide valuable insights and the most up-to-date information for those providing care to people with spinal cord injury (SCI) worldwide. The vision of the International Spinal Cord Society (ISCoS) is to "facilitate healthy and inclusive lives for people with spinal cord injury or dysfunction globally".
Contact us directly with any questions or comments at iscos@associationsltd.co.uk
Hello, I'm Michael Failings, professor of Neurosurgery at the University of Toronto. I'm Editor-in-Chief of Spinal Cord, which is the lead publication of the International Spinal Cord Society, or ISCOS, and is a Nature publication, and I'm joined today by Intisar Mohsin and Esma Bilarbi, who are senior high school students from Esmaus College in Rotterdam, the Netherlands, and this podcast is part of an ongoing series that I lead in my role as Editor-in-Chief of Spinal Cord, and today's podcast is really intended to disseminate the topic of spinal cord injury to the general medical health sciences and lay community, and usually I'm the one interviewing um uh colleagues on the podcast, but today there's going to be a slight role of reversal and intisar and esma will ask me some questions related to the um overarching topic of um spinal cord injury, with a particular focus on regenerative therapeutics, including stem cells. So, indisar and Esma, welcome to our podcast and I look forward to our discussion.
Speaker 2:Thank you so much. We're also looking forward to it. So to jump right in, we would like to ask you what is spinal cord injury in general?
Speaker 1:Yes, so spinal cord injury occurs when there is a traumatic injury to the spine that often will result in a fracture or disruption of the spinal cord.
Speaker 1:The injury can occur from either a penetrating injury related to violence, from a gunshot wound, a knife wound, but more commonly occurs from a blunt injury, including falls, motor vehicle collisions, sports, sports injuries and so on.
Speaker 1:The spinal cord is the connection from the brain to the body and it sends the key messages from the brain to the body, and when the spinal cord is injured, there is a disruption of the flow of these signals, and so, for example, if an injury occurs in the cervical area, in the neck, this can result in loss of motor and sensory function below the injury, so people can have weakness in the hands and the arms and the legs. That's referred to as tetraplegia and this can also have very significant impact on other functions, including control of ball, a bowel and bladder function, as well as autonomic a function, that is, the control of the organs such as the heart, and so there can be a cardiovascular dysfunction. Another type of spinal cord injury occurs from non-traumatic types of injuries. We refer to this as non-traumatic spinal cord injury, and one of the commonest causes of this relates to complications from degenerative arthritis or spondylosis of the spine, and this condition is called degenerative cervical myelopathy.
Speaker 2:Thank you so much, and could you also shortly explain what the difference is between a complete spinal cord injury and an incomplete spinal cord injury?
Speaker 1:differences between a complete spinal cord injury and an incomplete spinal cord injury. Yeah, so the definition of a complete or an incomplete spinal cord injury is quite critically important and this is a clinical definition and this has important aspects to it in terms of the functional impairment an individual will have in their prognosis for recovery. A complete spinal cord injury is where there's a complete loss of descending motor signals and ascending sensory signals and so someone has a complete paralysis of their muscle function below the level of the injury and they also have a complete loss of sensation below the injury. And then we use an impairment scale called the American Spinal Injury Association scale, which has now been adopted by the international standards and that would be referred to as an ASIA-A spinal cord injury.
Speaker 1:There are now different forms of incomplete injury, including what's called an ASIA-B injury, where there's a sensory sparing below the level of the injury but an individual still has complete paralysis. Such an injury has a fairly high rate of spontaneous recovery that can occur. So this is important. And then an ASIA-C and an ASIA-D injury are ones where there is a partial recovery of motor function, with an ASIA-D having better muscle control, and most patients who have an ASIA-D type of an injury are able to recover substantial independence, but any degree of recovery in the setting of a spinal cord injury can have an important impact on the affected individual yeah, thank you so much for cleaning that up for us.
Speaker 2:And um what kind of which current treatments, uh for spinal cord injury are currently available?
Speaker 1:yes, so we can break up the uh, the management or the treatments, into the acute phase of the injury, right after the injury occurs, then into the subacute phases, where an individual will typically go into rehabilitation, and then ongoing management of the injury when an individual goes back into the community. A key principle related to the acute management is a concept that time is spine. So spinal cord injury is a time-critical event and it's important to take the individual from the accident scene, protect their spine on a backboard, administer intravenous fluids and oxygen and then to transport that person to a spinal cord injury center. Person is imaged to define the injury and typically surgery should be done as early as possible, but within 24 hours after injury, to take the pressure off the injured spinal cord and to stabilize the spinal column and, concomitant with this, we pay particular attention to the blood pressure to maintain the perfusion to the spinal cord. That's referred to as hemodynamic management and there are some medications which are now considered to be options that the physician may consider. One is a corticosteroid medication called methylprednisolone to reduce the swelling and inflammation in the spinal cord, and a new drug that has just emerged which is showing promise is a sodium glutamate antagonist, riluzole.
Speaker 1:After the acute management of a spinal cord injury, usually within a couple of weeks after the injury, an individual is transferred to a rehabilitation setting and there the management there is to try to enhance the independence of such an individual. Depending upon the level of the injury, this may involve exercises to try to enhance a functional recovery of muscle function, and it may also involve the individual learning to use assistive devices, sometimes a wheelchair or, if there's a better function, a walker and so on, and there's really a very multidisciplinary rehabilitation management. And then in the community there's ongoing management required of people with spinal cord injury, because this is a lifelong condition that can affect many systems of the body and often a major issue for people longer term relates to control of bowel and bladder function, and so the management of the neurogenic bladder is an important issue. Really, a spinal cord injury affects virtually all body systems, and so a very holistic, multidisciplinary approach is required.
Speaker 2:Thank you so much. And there are obviously some new ways of treating spinal cord injury. Could you also explain that for us?
Speaker 1:Yes, there's a tremendous amount of emerging research related to spinal cord injury. So, from the acute period, what has emerged is the role and timing of early surgical intervention, the role of hemodynamic management, and there's ongoing research on how to optimize spinal cord perfusion. There's a lot of research that's going on in terms of medical treatments that could reduce the secondary injury of nerve cells after spinal cord injury, and a drug that has just emerged is the sodium glutamate antagonist, riluzole. There's a lot of research that's going on also related to the study of drugs and molecules that will overcome some of the inhibitory influences in the spinal cord that prevent nerve cell regeneration. So there's active research related to a blocking inhibitory molecule called NOGO, and the European colleagues in EMSCI have recently published a phase two study suggesting some benefits of this kind of an approach. And there's currently ongoing studies which are looking at trying to block other inhibitory factors, including repulsive guidance molecule A or RGMA, as well as blocking some of the scar factors in the injured spinal cord.
Speaker 1:Another very active area of research relates to the topic of neuromodulation. Area of research relates to the topic of neuromodulation and this relates to the delivery of electrical signals to the spinal cord to activate some of the residual circuits and to try to enhance function. And there has been recently approval of a treatment for people with an incomplete cervical injury, where electrical stimulation is applied percutaneously to the skin to enhance the function in the hands in upper extremities. And then, of course, a big topic of future research relates to the use of other regenerative therapeutics, including stem cells and bioengineered scaffolds.
Speaker 2:Yeah, so there's obviously a lot of new research going on. And how could stem cell therapy? How is it expected to work in repairing or supporting recovery in patients with a spinal cord injury?
Speaker 1:Yeah, so there's been a lot of interest in stem cells and there's, you know, there have been tremendous advances in the field. But unfortunately this has also been the subject of a lot of hype, and of course there's a lot of hope, and so there has been a lot that's been written in the lay press and on various claims that have been been made related to to stem cells. But the reality is is that there have been tremendous advances in the use of stem cells. To date there is no established stem cell therapy, so stem cells are only to be studied in clinical trials and individuals should not be charged for the use of the stem cells. And it's also very important that individuals who receive a stem cell treatment are followed very carefully, kind of long term.
Speaker 1:So what is a stem cell? So a stem cell is able to self-replicate in perpetuity, and stem cells can either be multi-potential or pluripotential or omnipotential, and an example is an embryonic stem cell that can make many different types of cell lines. But for spinal cord injury, there's been a lot of interest in what are referred to as committed neural stem cells, and so these are stem cells that are committed toward a neural fate, so they can make neurons, astrocytes and oligodendrocytes, and there's now been a lot of research which has gone away from embryonic stem cells, which is really no longer really the current advanced type of technology, and there's been a tremendous amount of interest in the use of induced pluripotent stem cells, and this is based on the seminal Nobel Prize winning discovery of Professor Yamanaka from Japan, and this is where a somatic cell, such as a skin cell, can be transformed into an induced pluripotent stem cell with the delivery of various transcription factors. But it's very important that this be done in a very controlled, precise fashion. There have been preliminary clinical trials with the use of committed neural stem cells which have shown promise, but to date the extent of a beneficial effect has not been sufficient to warrant this being a clinical treatment.
Speaker 1:And right now there's been a lot of intensive research in regenerative neuroscience laboratories to overcome some of the problems that have occurred with stem cells. That have occurred with stem cells. These include poor survival and trying to overcome the inhibitory influences in the spinal cord, such as the scar tissue that's in the spinal cord, and then also trying to figure out how to drive these neural stem cells to make neural circuits, neural stem cells to make neural circuits, and so there is a lot of advances that have occurred in the last several years and it is anticipated that over the next five years or so there will be a resurgence of clinical trials looking at advanced engineered neural stem cells advanced engineered neural stem cells.
Speaker 2:Oh, wow, that's really interesting because we also were thinking that the embryo stem cells would be would have the most potential, but apparently not. This is like totally information for us. But, um, there are obvious. There will obviously be barriers and like obstacles with uh applying these stem cells. Uh, what could those barriers and like obstacles with applying these stem cells? What could those barriers and or obstacles be?
Speaker 1:I think that's an important question and probably a good way to sort of frame the conclusion of our discussion. Conclusion of our discussion. So one of the important factors to consider relates to safety, and one of the critical reasons why individuals seeking potential stem cell therapies should only be enrolled in a carefully controlled clinical trial. And this is because if an individual were to receive, say, an uncontrolled embryonic stem cell, there's a potential that this could make a tumor or even a cancer, and so this is very, very important, that the stem cell be very carefully defined. And so there's a lot of safety considerations.
Speaker 1:Then there are challenges with the delivery of the stem cells, and for neural stem cells they need to be surgically delivered, and there's been a lot of research that's being done now in terms of trying to deliver this through a less invasive kind of an approach, but this still involves a surgical delivery to the injured spinal cord.
Speaker 1:And then there are biological challenges in terms of trying to overcome the inhibitory factors in the injured central nervous system, and then this will need to be combined with kind of targeted rehabilitation approaches.
Speaker 1:So there's a number of challenges and opportunities, but this is an extremely promising area. So on that note, I think I'm going to bring the podcast to a close. It's been a pleasure speaking with two very bright high school students from Esmos College in Rotterdam, netherlands, into Sarmocene and Esma Bilarbi, and, in summary, we have been discussing the whole topic of spinal cord injury and, in broad strokes, we've tried to define the area and and to really to make this more accessible to a lay audience into a general health care community. There have been tremendous advances that have occurred in the clinical management of a spinal cord injury and the future appears to be very bright related to ongoing research, and I would encourage all of you who wish to stay attuned to advances in spinal cord injury to follow us on Spinal Cord, which is the lead journal of the International Spinal Cord Society, or ISCOS. And on that note I'd like to close out the podcast and thank you again, intisar.
Speaker 2:Thank you so much. Thank you, you too.