Scientists reverse stroke damage with stem cell therapy

Scientists have achieved a significant breakthrough in stroke recovery, using stem cell therapy to repair stroke damage in mice

In a landmark study, researchers at the University of Zurich have successfully reversed stroke damage in mice by transplanting human neural stem cells into the injured brain. The grafted cells not only survived and matured into functioning neurons but also stimulated blood vessel growth, reduced inflammation, and contributed to rebuilding the blood-brain barrier. Most strikingly, the treated mice regained motor abilities, offering a glimpse of how stem cell therapy might one day transform stroke recovery in humans.

New therapies for stroke recovery are vital

One in four adults will experience a stroke in their lifetime, with lasting effects of residual damage such as paralysis or speech impairment. Currently, no treatments exist to repair this kind of damage.

“That’s why it is essential to pursue new therapeutic approaches to potential brain regeneration after diseases or accidents,” said Christian Tackenberg, the Scientific Head of Division in the Neurodegeneration Group at the University of Zurich (UZH) Institute for Regenerative Medicine.

Now, researchers have taken neural stem cells and regenerated brain tissue, with two studies supporting this thesis.

Reversing stroke damage in mice

The researchers used human neural stem cells, from which different cell types of the nervous system evolve. The stem cells were derived from induced pluripotent stem cells, which in turn can be manufactured from normal human somatic cells.

The team induced permanent stroke in mice, which has characteristics that commonly resemble stroke in humans. The animals were also genetically modified to accept the human stem cells.

One week following the stroke, the researchers transplanted neural stem cells into the injured brain region and observed subsequent developments using a variety of 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 added.

The brain regenerates itself

The researchers found other markers of brain regeneration, including the formation of new blood vessels, an attenuation of inflammatory response processes, and improved blood-brain barrier integrity.

“Our analysis goes far beyond the scope of other studies, which focused on the immediate effects right after transplantation,” Tackenberg explained.  Fortunately, stem cell transplantation in mice also reversed motor impairments caused by stroke. Proof of that was delivered in part by an AI-assisted mouse gait analysis.

The future of stroke treatment could be stem cell therapy

Tackenberg aims to bring this exciting development to humans eventually, and this was at the forefront of his research. To ensure its efficacy on humans, the team used stem cells that were manufactured without the use of reagents derived from animals.

The Zurich-based research team developed a defined protocol for that purpose in collaboration with the Center for iPS Cell Research and Application (CiRA) at Kyoto University. This was crucial to ensure the success of stem cell therapy in humans.

The team also found that stem cell transplantation works better when performed not immediately after a stroke, but a week later, as the second study verified. In the clinical setting, that time window greatly facilitates therapy preparation and implementation.

Despite the encouraging results of the studies, Tackenberg cautions that further work is needed. “We need to minimise risks and simplify a potential application in humans,” he says. Tackenberg’s group, again in collaboration with Ruslan Rust, is currently working on a 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.”