A study recently published in Nature Communications from the University of Zurich has shown that the transplantation of stem cells can reverse stroke damage by regenerating neurons, which restores motor functions and repairs blood vessels. Not only did this breakthrough heal mice with stroke-related impairments, but it also suggests that treatments such as this could be adapted for humans to move towards tackling the damage done from one of the World’s most devastating brain disorders.
Statistics estimate that 1 in 4 adults will suffer a stroke in their lifetime, and half of them will be left with residual damage like paralysis or a speech impairment because of internal bleeding or the lack of oxygen that occurs during the event, killing brain cells irreversibly. Currently, there are no available therapies that exist which can repair this kind of damage.
“That’s why it is essential to pursue new therapeutic approaches to potential brain regeneration after diseases or accidents,” says Christian Tackenberg, the Scientific Head of Division in the Neurodegeneration Group at the University of Zurich (UZH) Institute for Regenerative Medicine.
“Our findings show that neural stem cells (neural stem cells have the potential to regenerate brain tissue) not only form new neurons, but also induce other regeneration processes,” Tackenberg says.
From Stem Cells to Neurons
For this study, human neural stem cells were utilized from which different types of the nervous system can form. The stem cells were derived from induced pluripotent stem cells, which can be manufactured from human somatic cells. When the stem cells were manufactured, it was done so without the use of reagents derived from animals. Mice were genetically modified to not reject human stem cells, and they were induced into a permanent stroke state that closely resembles the manifestation in humans. One week after inducing the stroke state, the neural stem cells were implanted into the injured brain regions to observe the subsequent developments using various imaging and biochemical methods.
“We found that the stem cells survived for the full analysis period of five weeks and that most of them transformed into neurons, which actually even communicated with the already existing brain cells,” Tackenberg says.
Other markers of regeneration were also found, such as the new formation of blood vessels, which is an attenuation of inflammatory response processes and improved blood-brain barrier integrity. The stem cell transplantation was also observed to reverse the motor impairments that were caused by stroke, proof of which was evidenced in part by mouse gait analysis.
“Our analysis goes far beyond the scope of other studies, which focused on the immediate effects right after transplantation,” Tackenberg explains.
A defined protocol was developed for developing stem cells without the use of reagents derived from animals during this study, which is important for potential therapeutic applications in humans. Another important insight from this study was that stem cell transplantation for stroke recovery works better when it is performed a week after stroke rather than immediately after a stroke. This window of time would facilitate the preparation of the therapy and its implementation.
More Research Required
Despite the promising results, the researchers caution that there is still much more work to be done. “We need to minimize risks and simplify a potential application in humans,” he says. Tackenberg’s group, again in collaboration with Ruslan Rust, is currently working on a kind of safety switch system that prevents the uncontrolled growth of stem cells in the brain. Delivery of stem cells through endovascular injection, which would be much more practicable than a brain graft, is also under development. Initial clinical trials using induced stem cells to treat Parkinson’s disease in humans are already underway in Japan, Tackenberg reports. “Stroke could be one of the next diseases for which a clinical trial becomes possible.”
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