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Stem Cell Therapy for Strokes
Neurological repair and the restoration of function are now possible with stem cell therapy.
Stem cell therapy has been repeatedly shown to be an effective treatment in the repair of neurological damage caused by stroke. Stem cell therapy offers great promise for stroke victims. Stem cells can be used to repair damaged brain tissue which results after a stroke. Victims of stroke can regain movement, senses and understanding from stem cell transplants.
At the Stem Cell Institute and the Department of Neurosurgery at the University of Minnesota, researchers have demonstrated the ability of transplanted stem cells to restore function in rats who have suffered strokes. The stem cells were isolated and expanded from bone marrow and then transplanted into rats seven days after an ischemic stroke injury to the brain. Before the stem cell transplant, the rats were unable to use their forelimbs and hind limbs properly. After the stem cell transplant, the rats regained proper use of their limbs. In this study the transplanted stem cells were found to develop into cells that exhibited characteristics of neurons, astrocytes and oligodendroglia, which are the major types of brain cells. These findings show that stem cells obtained from adult bone marrow are effective in repairing the brain and restoring lost function after a stroke. The brain has built-in mechanisms for repairing itself after any type of damage, and with added stem cells the probability of recovery is improved. The stem cell transplants also appeared to increase the production of a key protein in the brain known as "ApoE", which helps the brain repair itself and form new links between the damaged and undamaged tissues. The next steps in the research will be to determine how long after a stroke has occurred will the stem cell transplant therapy still be effective, and also whether or not bone marrow stem cells are able to maintain a stable neural phenotype over prolonged periods.
At the American Heart Association's 24th International Conference on Stroke and Cerebral Circulation, Frank Sharp, M.D., from the Department of Neurology at the University of California at San Francisco, reported the results of research conducted with naturally-occurring stem cells in the brains of rodents. The researchers observed a 12-fold increase in the growth of new cells in the brains of the rodents, following strokes that had occurred in the hippocampus, where memory is controlled. Long-term memory is stored in the dentate gyrus of the hippocampus, and naturally occurring stem cells remain in the brain next to the ventricles and in the hippocampus throughout life. These stem cells were found to differentiate into neurons and astrocytes following the ischemia in the rodents.
In a similar study, a research team from Stanford University has injected stem cells into the brains of rats with stroke damage. They found that the stem cells could migrate to the damaged areas of the brain and differentiate into the right type of brain cells. The doctors believe signals from the damaged cells act as a "distress call", beckoning the transplanted stem cells toward their target, while other signals are believed to direct the stem cells in their transformation into neurons and supporting astrocytes.
In the ongoing research on regeneration, scientists at Harvard Medical School and Children's Hospital in Boston have identified a protein, which they named "Troy", which is responsible for inhibiting myelin formation and axonal regrowth in the human central nervous system (CNS). (From Neuron, February 3, 2005, Vol. 45, pp. 345-351). One of the reasons why the repair of brain and spinal cord injuries has always been so difficult is that certain inhibitory molecules which are associated with myelin in the CNS are also responsible for blocking the regeneration of this type of nerve cell. Myelin is a fatty coating that forms a protective sheath around axons by spiraling plasma membranes of Schwann cells in the peripheral nervous system and oligodendrocytes in the central nervous system. The inhibitory proteins associated with myelin sheaths are often also involved in inflammatory responses and in a complex series of other cellular events. Understanding the obstacles to neuronal regeneration means that we are that much closer to removing these obstacles. This research which identified the "Troy" protein was funded by NINDS, who announced that the results of this finding hold great potential for the treatment of all types of CNS damage, such as stroke, multiple sclerosis, and traumatic spinal cord injury. In combination with a safe and effective treatment such as stem cell therapy, discoveries such as this offer great promise for the treatment of a wide range of diseases which previously have had no reliable form of treatment.(From the website of the National Institute of Neurological Disorders and Stroke).
A connection exists between inflammatory responses and demyelination, although this link is not yet fully understood. Nevertheless, it has been found that immunoglobulin therapy consisting of high-dose intravenous immunoglobulin (IVIg) is effective in the treatment of inflammatory demyelinating disease. The immunoglobulin treatments protect oligodendrocyte precursor cells and oligodendrocytes by inhibiting inflammatory mechanisms. While stroke is neither considered to be an inflammatory nor a demyelinating disease, remyelination is nevertheless a factor in the regeneration of neuronal tissue that has been damaged by stroke. Additional modes of treatment such as those involving the ciliary neurotrophic family (CNTF) as well as glial growth factor 2 (GGF2) have been found to be useful in promoting the proliferation, maturation and survival of oligodendrocytes, which in turn have been shown to promote remyelination. Such considerations, when combined with stem cell therapy, offer great promise in the treatment of neurological conditions such as stroke.
It has been found that if stem cell therapy is administered to a stroke patient who also suffers from other tissue damage not directly related to the stroke, the stem cell therapy will also target and repair the other injuries, in addition to those caused by the stroke. One such example was a male stroke patient who also suffered from prostate cancer. After receiving the stem cell treatment for his stroke, his PSA dropped from 7.9 to 2.6 in 3 months.
In a Congressional testimony in March of 2006 before the House Subcommittee on Labor, Health and Human Services, and Education Appropriations, Dr. S.C. Landis, the Director of the National Institute of Neurological Disorders and Stroke (a division of NIH), as part of his budget request for Fiscal Year 2007, made the following statement:
"The mission of the NINDS is to reduce the burden of neurological disorders by developing ways to prevent or treat these diseases ... Stroke, dementias, chronic pain, and Parkinson's disease will increase, if unchecked, with the aging of our population. The impact of neurological disorders on people, on their families, and on our economy is immense." (From the website of the National Institute of Neurological Disorders and Stroke).
"Translational research" - the process by which the results of basic research are "translated" into clinical trials and practical therapies - is one of the primary areas of funding by NINDS. In his 2006 Congressional testimony, Director Landis identified stem cell therapy as one of the major fields of greatest importance in translational research.
The medical profession today incorporates many diverse disciplines into the investigation of any disease: basic science research, neuroscience tools and genome analysis, imaging technology and proper clinical assessment, to name just a few, are among the many components that constitute the formal diagnosis and assessment of neurological conditions such as stroke. As a treatment which is founded upon the most rigorous of scientific principles and techniques, stem cell therapy offers a safe and effective option for stroke patients, for whom no such options have previously existed in the past.
Stroke Overview
According to the National Institute of Neurological Disorders and Stroke (NINDS, part of the National Institutes of Health), a stroke is defined as follows:
"A stroke occurs when the blood supply to part of the brain is suddenly interrupted or when a blood vessel in the brain bursts, spilling blood into the spaces surrounding brain cells. Brain cells die when they no longer receive oxygen and nutrients from the blood or there is sudden bleeding into or around the brain. The symptoms of a stroke include sudden numbness or weakness, especially on one side of the body; sudden confusion or trouble speaking or understanding speech; sudden trouble seeing in one or both eyes; sudden trouble with walking, dizziness or loss of balance or coordination; or sudden severe headache with no known cause. There are two forms of stroke: ischemic - blockage of a blood vessel supplying the brain, and hemorrhagic - bleeding into or around the brain."
(From the website of the National Institute of Neurological Disorders and Stroke).
The best treatment for stroke, as with any malady, is prevention, since there has not previously existed a reliable treatment for the type of neurological damage that results from stroke. The most effective treatments that can be administered to stroke victims must be administered within the first few minutes after the stroke has begun, and oftentimes this is not possible. The class of drugs known as thrombolytics and antithrombotics (anticoagulants and antiplatelet agents) were developed primarily for the prevention of stroke, although they are also administered after a stroke has occurred, with varying degrees of success. Medications used in the treatment of hypertension, atrial fibrillation and diabetes are also typically used to prevent a first or recurrent stroke in people who exhibit these risk factors. Some "acute stroke therapies" have been developed which attempt to stop a stroke while it is happening, by quickly dissolving the blood clot which is causing an ischemic stroke, or by quickly halting the bleeding of a hemorrhagic stroke, but not everyone who suffers a stroke is able to receive these therapies in time.
The prognosis for the individual after a stroke has occurred can depend upon a variety of factors. It is not uncommon for stroke patients to suffer "hemiplegia", which is a complete paralysis on one side of the body, or "hemiparesis", which is a weakness on one side of the body. All cognitive abilities, including, most noticeably, speaking and memory, may be damaged, and physical impairments may also result. A lack of emotional control may be seen, and many stroke patients suffer from depression.
Some people may recover from a stroke and return to relatively normal lives, while other individuals may die due to a very severe stroke.
According to NINDS, recurrent strokes are frequent, with about one-fourth of all people who recover from their first stroke having another stroke within 5 years.
Ischemic stroke accounts for 83% of all strokes and occurs as a result of an obstruction within a blood vessel that supplies blood to the brain. Hemorrhagic stroke accounts for the remaining 17% of all stroke cases and results from a weakened vessel that ruptures and bleeds into the surrounding neurological tissue. "Transient ischemic attacks", or "T.I.A.s", are considered to be minor strokes; they result from the same conditions which cause an ischemic stroke, but the obstruction tends to resolve by itself, usually in a short period of time, and without noticeable damage.
A stroke may be diagnosed through an assessment of one's medical history in combination with a physical and neurological examination that may include blood tests and some imaging such as a CT scan.
A stroke is a medical emergency and warrants immediate attention, which is crucial to recovery. Any delay in seeking treatment may increase the risk of damage and decrease the likelihood of recovery.
52% of stroke patients are unaware that they are experiencing a stroke. About 700,000 Americans suffer a new or recurrent stroke every year. Stroke kills nearly 163,000 people per year in the U.S., and is ranked as the 3rd leading cause of death. About every three minutes someone will die of a stroke, with about two-thirds of the deaths occurring in men.
One of the dangers of stroke is the "cascading" series of events that it triggers. When a stroke occurs, brain cells in the immediate area usually die within minutes to hours, thereby releasing chemicals that set off a series of chain reactions known as "ischemic cascade". (Ischemic cascade may also result from a hemorrhagic stroke, as well as from an ischemic stroke). This process endangers brain cells not only in the specific locus of the ischemia or hemorrhage, but also in the larger, surrounding areas of the brain tissue. Without prompt medical attention, this larger area of brain tissue will also be damaged. Given the rapid pace of the ischemic cascade, medical intervention is required within the first 6 hours after the stroke in order to reestablish blood flow and for neuroprotective agents to be effective. Clotting factors known as "VII" and "VIIa" have shown promise for the more severe strokes that are caused by extensive hemorrhage, from which hematomas typically form, and from which disability and even death often result.
In the United States, NINDS is the primary supporter of biomedical research on the brain and the nervous system in general. As of 2006, NINDS currently supports more than 1,000 clinical research projects throughout the country, of which more than 125 are clinical trials involving the prevention and treatment of neurological disease. In addition to conducting their own research and clinical trials at their own laboratories and clinics at NIH (the National Institutes of Health), NINDS is also the primary funder of major grants to major medical institutions throughout the U.S. for the study of stroke. Primary areas of research include genetic and environmental risk factors, and the processes by which brain damage results from stroke. In 2005, a NINDS clinical trial showed that aspirin prevents stroke effectively for people who have partially blocked arteries in the brain and who have had a previous stroke or T.I.A.; indeed, the study showed aspirin to work as effectively as ticlopidine and warfarin, the latter being a drug which requires monthly monitoring and which carries the risk of major hemorrhage and heart attack.
As in any disease, genetics plays a role, and one's proclivity for stroke is no exception. NINDS has therefore also funded the development of "GENSAT" (Gene Expression Nervous System Atlas), which maps the genetics of the nervous system, in an effort to better understand the correlation between specific genes and their corresponding neuro-physiological pathologies.
People of any age, including children, can suffer a stroke. According to the National Stroke Association, the rate of occurrence of stroke in children in the U.S. is approximately 3 cases in every 100,000 children per year, with the incidence being the highest in children under the age of 2. (From the NSA - National Stroke Association website).
It takes the average adult between 12 and 24 hours to reach a hospital after recognizing the symptoms of a stroke; in children, the average response time is 48 to 72 hours. Indeed, many strokes in children go unrecognized, due to the widespread yet erroneous belief that children cannot suffer strokes.
Instead of being caused by high blood pressure, high cholesterol, a history of smoking, too much alcohol or obesity, as is the case with adults, strokes in children are often caused by birth defects, infections (such as meningitis or encephalitis), trauma, or blood disorders such as sickle cell anemia. As with adults, however, children may also have difficulty with speech and memory both during and after the stroke, and they may show paralysis or weakness on one side of the body. Lasting disabilities in children who have had strokes may include cerebral palsy, mental retardation or epilepsy. Even immediately after birth, and before birth while still in utero, infants can suffer strokes. This has been identified as one of the causes of cerebral palsy.
Depending on the age and developmental stage at which a child suffers a stroke, he or she may be able to recover. Nevertheless, regardless of the age of an individual, and regardless of whether someone is a child or an adult, identification and treatment of the stroke are of the utmost importance. As described on the website of the National Stroke Association, the acronym "F.A.S.T." may help people recognize if someone, whether a child or an adult, is having a stroke:
- Face: Ask the person to smile. Does one side of the face droop?
- Arms: Ask the person to raise both arms. Does one arm drift downward?
- Speech: Ask the person to repeat a simple sentence. Are the words slurred? Can the person repeat the sentence correctly?
- Time: If the person's responses to these questions are not normal, time is of the essence, as brain cells may be dying. Medical help should be sought immediately.
(From the NSA - National Stroke Association website).
The U.S. Centers for Disease Control and Prevention estimate that the death rate from stroke declined by 18.5% between 1993 and 2003 for the U.S. population. (From the website of the CDC - Centers for Disease Control and Prevention). Regardless of the statistics, however, there seems to be widespread agreement among scientists and clinicians that the development of therapies which can help the brain repair itself, and which can restore lost function to the individual, are what is most needed.
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