Ischemic stroke, also called a cerebrovascular accident, is caused by interrupted or decreased blood supply to a portion of the brain. Around 40 million people globally suffer from some form of stroke, and survivors are often disabled, impacting the patient’s and family’s quality of life. The main clinical manifestation of stroke is the ischemic (damaged) brain tissue also has a reduced number of neurons, interrupted neural axon network, and disabled brain function. Around 5% of stroke patients receive tissue plasminogen activator (tPA), which can prevent physical disabilities.
Stem cell research has shown that patients with ischemic stroke can benefit from infusions and therapy with stem cells. Stem cells have high self-differentiation and self-replication potentials, which means they can transform into neural (nerve) stem cells. These cells also can differentiate into astrocytes, oligodendrocytes, and neurons, which are necessary structures for brain function. At present, there are few studies involving human subjects, because of safety and ethical issues. However, animal research is promising.
Research regarding Use of Stem Cells
In a large review of clinical studies, researchers identified 16 randomized controlled trials and 18 independent treatment studies involving stem cell therapy for patients with brain ischemia. The results of the review found that stem cell transplantation therapy could significantly improve neurological deficits and patient quality of life. In addition, there were no serious adverse events noted due to stem cell therapy. The improved recovery mechanism of action is thought to involve successful synaptic integration, with stem cells replacing lost neurons and circuits. In addition, beneficial effects occur involving immunomodulation, neural plasticity, endogenous neurogenesis, and neovascularization.
Stem cell transplantation in animal models with ischemic brain injury have shown beneficial effects. In one study, human blood and mesenchymal stem cell transplantation in animal models with brain damage improved behavioral outcomes. Researchers found remyelination, as the cells transformed into neurons, oligodendrocytes, and endothelial cells to replace damaged structures. In another study, use of autologous bone marrow and umbilical cord stem cells were found to reduce the risk for immune rejection. Researchers postulated that if the cells were infused or transplanted soon after the cerebrovascular accident, the greater the benefits.
In a study involving 26 patients with a stroke, intracranial transplantation was proven safe. During a 6-month evaluation period, functional benefit was evaluated in comparison to a control group. Researchers found that the patients who received stem cell therapy had significant improvements. Another trial using bone-marrow stem cells demonstrated feasibility and safety, and it involved IV therapy. The first large clinical trial involved 97 patients with ischemic stroke, and results showed improvement in motor functions.
Factors that Influence Efficacy of Stem Cell Therapy
In many clinical studies, larger cell numbers infused or transplanted were not associated with increased efficacy. Most experimental data have been generated from transplantation of the stem cells within 24 hours of the actual stroke onset. However, stem cell therapy initiated up to 4 weeks post-stroke had proven to significantly improve functional recovery. Acute delivery (right after the stroke, or within 24 hours) is thought to be essential.
The mode of stem cell delivery can be influenced by certain factors, including timing, type of cell used, and safety/efficacy profiles. Intracerebral transplantation is thought to work best, but has a higher risk profile due to the invasive nature of the procedure. However, systemic deliver (intravenous or IV) has proven to be safer and more feasible than transplantation through open method. Experts believe that the therapeutic advantage of transplantation is local release of cell-secreted paracrine molecules and helpful proteins in the brain infarct region. However, regarding safety, infusion seems to be the preferred mode of delivery.
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Chen L, Zhang G, Khan AA, et al. (2016). Clinical Efficacy and Meta-Analysis of Stem Cell Therapies for Patients with Brain Ischemia. Stem Cells Int, 6129579.
Lemmens R & Steinberg GK (2015). Stem cell therapy for acute cerebral injury: What do we know and what will the future bring? Curr Opin Neurol, 26(6), 617-625.
Martino G., Pluchino S. The therapeutic potential of neural stem cells. Nature Reviews Neuroscience. 2006;7(5):395–406. doi: 10.1038/nrn1908.
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The most revolutionary regenerative medicine treatments now being offered include amniotic and umbilical stem cell treatments. These are FDA regulated and contain growth factors, hyaluronic acid, cytokines and stem cells.