- The central nervous system does not routinely regenerate after damage so the disability caused may be permanent and profound.
- There is only a small window of opportunity – hours, maybe weeks – in which therapies may reduce the disability caused by spinal cord injuries.
- Restoring the electrical transmission between the brain and spinal cord requires repairing the myelin sheath (insulation) around damaged nerves, and in severe cases, the regrowth of severed nerve fibres across the site of injury and into the neural network below the damage.
How can stem cells play a part?
The basis of using stem cells to treat spinal cord injury would be as a source of new cells and products that could prevent further spinal cord damage, restore nerve function, generate new nerve cells and guide the regrowth of severed nerve fibres. Stem cells have an unparalleled regenerative capacity with the flexibility to grow into hundreds of different cell types and make factors that can support a range of physiological functions. Researchers are evaluating which types of stem cells are the best for growing neurons and other support cells in the brain, and making factors that promote nerve function. They want to develop strategies that transplant the support cells that wrap myelin insulation around nerve fibres to conduct electrical signals. A steady supply of these cells grown from stem cells could be a tremendous asset for studies that are exploring how to restore nerve function across damaged spinal cords.
Two main strategies for using stem cells to treat spinal cord injury are being explored: exogenous and endogenous repair (exo meaning outside the body and endo meaning inside the body). In exogenous repair the required cells are first grown from stem cells in the laboratory and then transplanted into patients. In endogenous repair stem cells are transplanted into the patient and the outcome depends on the body's ability to coax the stem cells to grow into the required cells. Either way, the goal is to use stem cells to improve nerve function. There are no existing therapies that are able to repair spinal cord injuries.
Are there lots of groups working on developing a stem cell therapy?
Many research teams around the globe are working to develop stem cell therapies for spinal cord injury. Their common goals are to identify which stem cells are best suited for the job, which signals will be able to coax them into becoming neurons or support cells, and which large scale lab methods are effective at ramping up the production of the required cells.
The discovery of neural stem cells in Canada in 1992 kindled great hope among that stem cells could someday be used to regenerate the damage caused by spinal cord injury. Until around 1998, it was believed that the brain could not repair itself by regenerating new neurons. We now know that patients who have partial lesions to the spinal cord do experience a degree of spontaneous recovery arising from the ability of the brain to reorganize new connections. These observations spurred researchers to test their theories in animal models of spinal cord injury, and the positive results have provided the proof of principle that stem cells can potentially improve function after spinal cord injury.
Stem cell research is continuing on a number of different avenues and some of the successful stops along the way have yielded early Phase 1and 2 clinical trials for spinal cord injury. These trials are very small, mostly testing the safety of putting adult stem cells into patients. The results should yield information about the viability of this kind of therapy, but further clinical trials will be required to answer the question of whether a stem cell therapy can improve nerve function. For patients, the answer to that question is still many years away.
North American Study
A North American clinical trial is using adult neural stem cell injections to treat spinal cord injury. Find out more here.
Before basic stem cell research can be translated into the clinic it must first be rigorously tested and validated. For spinal cord injury, this involves transplanting stem cells, the cells they make (progeny) or factors that support neural growth (neurotrophic factors) into animal models to test if nerve conduction can be restored. As a prelude to these experiments, scientists are using animal models to develop laboratory cultures and drugs that can direct the growth of stem cells into different types of neural cells.
The road to finding a stem cell cure is paved with many challenges that will take time to overcome. There are as yet few clinical trials evaluating the safety and feasibility of using stem cells for treating spinal cord injury but the wealth of information generated from labs around the globe is converging to help with the transition from basic research to the clinic.
Current research using adult stem cells
Adult neural stem cells are able to make a range of cell types, including neurons that conduct nerve impulses and support cells that make myelin (called oligodendrocytes) or promote nerve function (called astrocytes). Scientists want to take advantage of this regenerative capacity. They are trying to develop ways to recruit the body's own neural stem cells or transplant other sources of neural stem cells into the injured spinal cord to supply a new source of cells to repair the damaged cord. Studies in rats are showing that transplanting oligodendrocyte and astrocyte precursors made from neural stem cells can repair axons – the long skinny highways that transport electrical impulses from one nerve to another – and decrease motor neuron loss.
Olfactory ensheathing cells are a unique population of cells that live in our nasal cavity. In a very exciting discovery, it was found that olfactory ensheathing cells are able to continually stimulate the regrowth of axons in the peripheral and central nervous systems. Transplanting these cells into animal models of spinal cord injury has shown some promise and scientists have hit on the technique of adding bioscaffolds to help direct axon cell growth and remodeling. There is currently one small Phase 1 trial assessing the safety of transplanting olfactory ensheathing cells into patients. Time will tell whether these cells have what it takes to provide growth factors that support and enhance the survival of neurons.
Current research using fetal stem cells
Researchers are very interested in tapping into the power of astrocytes for spinal cord injury. These star-shaped brain cells are extremely important for generating nerve fibre growth early in development, and they continue to provide a crucial support role to the brain and spinal cord throughout life. By manipulating different growth factors, scientists are now able grow two different types of astrocytes from fetal stem cells, one of which promotes recovery in animal models of spinal cord injury. This finding lends weight to the idea that growing a specific astrocyte pool is more successful than transplanting the fetal precursor stem cells. Fetal tissue is used only in proof-of-principle experiments and is not regarded as a suitable source of stem cells for potential therapies. In recent years, scientists have found alternate sources including umbilical cord blood and placenta, both of which are discarded at birth, and which contain a ready supply of fetal stem cells for research purposes.
Current research using embryonic stem cells
In nature, the master stem cell is the embryonic stem cell because it can make an entire human being. Scientists have devised methods for turning human embryonic stem cells into oligodendrocytes, which have been able to restore neural function in animal models of spinal cord injury. Translating these results into clinical trials is not as easy as it might seem because it is often tricky to make oligodendrocytes in the laboratory without also making other unwanted cell types or forming tumours. Researchers have found a way around this by first coaxing human embryonic stem cells to specifically become neural cells and then transplanting these more mature cells so that the chances of tumour formation are decreased. They have also showed that transplanting neural cells on a biodegradable scaffold provides a surface for them to cling to and helps with the release of beneficial growth factors.
Current research using induced pluripotent stem cells
Researchers have found a way to reprogram adult stem cells to behave like embryonic stem cells. These induced pluripotent stem cells or iPS cells ('pluripotent' from the Latin words 'very many' and 'having power') can be made from skin or other tissue cells. Researchers have shown they can turn iPS cells into neurons, oligodendrocytes and astrocytes. The great advantage of using iPS cells is that they are easily accessible and can provide a source of cells directly matching the genetic profile of the patient. Despite tremendous promise, however, there is a lot of work to do before iPS cells can be used for transplantation studies in humans.
Readers may wish to peruse the recommended sites and articles below for more information about spinal cord injury and the possible applications of stem cells to treat this disease.
Canadian Paraplegic Association (www.thespine.ca)
Christopher and Dana Reeve Foundation Paralysis Resource Center (http://goo.gl/KlryN)
Research Summary of Stem Cells and Spinal Cord Injury (http://goo.gl/bnJdW)
Rick Hansen Foundation (www.rickhansen.com)
Stem Cells for Spinal Cord Injury - Frequently Asked Questions (http://goo.gl/T7t0s)
UAB Spinal Cord Injury Model System Information Network (http://www.uab.edu/medicine/sci)