Are there stem cell therapies available for stroke?
To our knowledge, no stem cell therapy has received Health Canada or U.S. Food and Drug Administration approval for stroke treatment at this time. Patients who are researching their options may come across companies with websites or materials that say otherwise and offer fee-based stem cell treatments for curing this condition. Many of these claims are not supported by sound scientific evidence and patients considering these therapies are encouraged to review some of the links below before making crucial decisions about their own treatment plan. However, the field of stroke research is fast-moving and studies underway today may uncover new possibilities for more effective treatments tomorrow. Therefore, it is important to keep asking questions and continue seeking advice from qualified experts.
For more about stem cell clinical trials for stroke click here. (For printed version: http://goo.gl/YvlOf)
How close are we? What do we know about stroke?
- Stroke is a leading cause of adult disability worldwide and the second highest cause of death in the world. One in five stroke victims die and another third are left with permanent disabilities.
- The majority of strokes (85%) are ischemic, which means that blood flow to the brain is interrupted due to a blood clot. When this happens, different cell types in the brain are starved of essential nutrients and oxygen. Blood flow to the brain is restored very quickly during a transient ischemic attack (TIA), but brain cells will begin to die if the interruption lasts for minutes, resulting in a core zone of dying tissue called an infarct.
- Hemorrhagic stroke (15%) occurs when a rupture of a brain artery causes bleeding into the brain tissue, or when a brain aneurysm causes bleeding in between the brain and the tissue covering the brain and spinal cord.
- Risk factors for stroke include high blood pressure, irregular heartbeat, diabetes, smoking, carotid artery narrowing, high blood cholesterol, increasing age, and lifestyle factors (exercise, diet and alcohol).
- Preventive measures include a diet low in fat and sodium, controlling blood pressure and alcohol intake, maintaining a healthy weight, and regular exercise.
- Treatments for stroke are based on methods that restore the flow of blood to the brain, such as clot-busting enzymes, surgery, and drugs for thinning blood, stopping clots and protecting neurons.
- Death and disability are common outcomes of stroke because current treatments are not curative and the window of opportunity to administer treatments that restore blood flow is very short.
How can stem cells play a part?
Two main strategies underpin the exploration of stem cells as potential therapies for stroke. The first is endogenous (inside the body) repair. The point of endogenous repair is to stimulate stem cells that are already present in the brain and other parts of the body to heal damaged tissue. The second strategy is exogenous (outside the body) transplantation where stem cells are harvested, purified and then partially or completely differentiated into more mature cells to replace those that are lost, and then transplanted into patients.
Using stem cells to actually replace brain cells lost during stroke is a very long-term goal because many different cell types in the brain are destroyed, and transplanted cells will need to integrate and re-establish neural pathways that restore function to damaged areas. Scientists predict that it will take at least five to 10 years to determine if stem cell therapies can significantly improve the outcome for stroke victims. In the interim, stem cell therapies may be used to extend the window of opportunity for using drugs that salvage ischemic tissue, limit infarct size, break apart clots, and minimize inflammation or damage to brain tissue that sometimes occurs once blood flow is restored.
Are there lots of groups working on developing a stem cell therapy?
There are many research teams around the globe working to develop stem cell therapies for stroke. Their common goals are to identify which stem cells are best suited for the job, what is needed to mobilize endogenous stem cells or stimulate exogenous stem cells, the best route of delivery, the best post-stroke timing for delivery, and the endpoints used to measure whether the therapies are working.
One of the most important research contributions to date was in 1992 when Canadian researcher Samuel Weiss discovered that the brain has its own store of stem cells. These are hidden, as if in reserve, and much current research is being devoted towards figuring out how to coax these cells into repairing the brain after stroke.
Stem cell research for stroke is unfolding along a number of different avenues and some of the successful results are being translated into very early clinical trials. The majority of these test bone marrow stem cells, neural stem cells and mesenchymal stem cells. The trials underway are providing preliminary proof of the safety and potential effectiveness of the treatment, but there is still a long way to go before they show significant clinical changes for patients.
What research is underway?
Before basic stem cell research can be translated into the clinic for patients, it must first be rigorously tested and validated. For stroke, this involves transplanting stem cells into animal models to test if blood flow can be restored, working out how to stimulate endogenous stem cells, and tackling the problems of drug delivery. The main types of adult stem cells being considered are bone marrow stem cells, neural stem cells in the brain, mesenchymal stem cells in bone marrow and other tissues, and endothelial progenitor cells or EPCs that make the cells lining our blood vessels.
The road to finding a stem cell therapy for stroke is paved with many challenges that will take time to overcome. One of the biggest is the incredible heterogeneity (diversity in the conditions and causes) among stroke patients and how that may obscure the measurement of clinical results observed in trials. Nevertheless, the wealth of information generated from labs around the globe is converging to help with the transition from basic research to the clinic and researchers are very hopeful that a stem cell therapy for stroke will be someday become a reality.
Current research using endogenous stem cells (neural and bone marrow)
Scientists are trying to mobilize stem cells that live in the brain or bone marrow to come out of their hiding places to help with the aftermath of stroke. They have found that a growth factor called G-CSF can push hematopoietic (blood) stem cells from the bone marrow to enter the bloodstream where they track to areas of brain damaged by stroke. In rodent models, this process leads to functional recovery and the formation of new neurons and blood vessels. The precise reason for this is still not totally understood, but it is clear that the hematopoietic stem cells are not actually the ones making new neurons. Instead, scientists think that growth factors secreted by these stem cells stimulate the production of new blood vessels and sustain neurons that would otherwise have died. Another possibility is that the secreted growth factors are “switching on” neural stem cells in the brain to make new neurons. Clinical trials testing the ability of G-CSF to promote recovery in stroke patients are underway.
Researchers are also trying to devise drug delivery methods that are less toxic and less invasive. This search has produced a gel delivery system that can be injected onto the surface of the brain and which biodegrades once the job is done. Preliminary experiments have shown that this way of delivering erythropoietin (EPO), a drug that can stimulate neural stem cells to contribute to tissue repair after stroke, protects neurons, creates new neurons and helps to control local inflammation in mouse models of stroke. This technology may also prove to be a very useful tool for delivering drugs to other diseased areas of the central nervous system.
Current research using mesenchymal stem cells
Researchers are excited about the early results using mesenchymal stem cells in animal models of stroke. Mesenchymal stem cells are located in many different organs and tissues and can be found lining the blood vessels throughout the body. When transplanted into animal models, they can migrate to damaged areas and improve recovery. Scientists believe that mesenchymal stem cell protection may originate from the growth factors they release that promote growth of new neurons, regulate the immune system and stimulate the formation of new blood vessels. To boost the beneficial effects of transplanted stem cells, researchers are also genetically modifying the cells to pump out other factors known to enhance neural repair and this approach is gaining ground in mouse models of stroke.
In a five-year follow-up of a randomized study evaluating autologous (from the patient) mesenchymal transplants, researchers corroborated the safety of the procedure and showed a higher level of recovery in the treated group. They suggest that further pre-clinical and clinical studies will help to optimize the benefits and that ways to boost the positive effects could include transplanting these stem cells soon after the initial stroke, genetically modifying the stem cells, and conditioning patients prior to the transplants.
Current research using endothelial progenitor cells
Endothelial progenitor cells or EPCs mature into endothelial cells that line all the blood vessels throughout the body. The strategy for using EPCs as a therapy for stroke is that they will contribute to the formation of new blood vessels that supply ischemic tissue, and also minimize inflammation in the brain by restoring the endothelial lining of the blood-brain barrier that is compromised during stroke. Preclinical studies are encouraging. Transplanted EPCs from umbilical cord blood have been found in newly formed blood vessels in animal models of ischemic stroke. There are a few clinical trials underway to test the theories but much more work needs to be done to verify the safety and usefulness of EPCs for stroke victims. Future studies may also combine EPCs with small molecules that control cell death, an outcome that invariably accompanies ischemic stroke.