Stem cells repair mouse brains post-stroke
Regenerative medicine
University of Zurich
image:
This image shows a coronal section through the mouse brain after stroke and neural stem cell transplantation. The dashed circle indicates the stroke area. The neurite projections of the transplanted human cells are stained in dark brown. Neurites extend locally into the cortex (CX) but also via the corpus callosum (CC) into the other brain hemisphere.
view moreCredit: University of Zurich
Stem cell transplantation can reverse stroke damage, researchers at the University of Zurich report. Its beneficial effects include regeneration of neurons and restoration of motor functions, marking a milestone in the treatment of brain disorders.
One in four adults suffer a stroke in their lifetime, leaving around half of them with residual damage such as paralysis or speech impairment because internal bleeding or a lack of oxygen supply kill brain cells irreversibly. No therapies currently 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,” says Christian Tackenberg, the Scientific Head of Division in the Neurodegeneration Group at the University of Zurich (UZH) Institute for Regenerative Medicine.
Neural stem cells have the potential to regenerate brain tissue, as a team led by Tackenberg and postdoctoral researcher Rebecca Weber has now compellingly shown in two studies that were conducted in collaboration with a group headed by Ruslan Rust from the University of Southern California. “Our findings show that neural stem cells not only form new neurons, but also induce other regeneration processes,” Tackenberg says.
New neurons from stem cells
The studies employed human neural stem cells, from which different cell types of the nervous system can form. The stem cells were derived from induced pluripotent stem cells, which in turn can be manufactured from normal human somatic cells. For their investigation, the researchers induced a permanent stroke in mice, the characteristics of which closely resemble manifestation of stroke in humans. The animals were genetically modified so that they would not reject the human stem cells.
One week after stroke induction, the research team 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 says.
Brain regenerates itself
The researchers also found other markers of regeneration: new formation of 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 explains. 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.
Clinical application moving closer to reality
When he was designing the studies, Tackenberg already had his sights set on clinical applications in humans. That’s why, for example, the stem cells 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 is important for potential therapeutic applications in humans. Another new insight discovered was that stem cell transplantation works better when it is performed not immediately after a stroke but a week later, as the second study verified. In the clinical setting, that time window could greatly facilitate therapy preparation and implementation.
Despite the encouraging results of the studies, Tackenberg warns that there is still 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 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.”
Human neural stem cells in culture. Cell nuclei are stained in blue, the neural stem cell-specific filament protein Nestin is shown in green, and the neural stem cell transcription factor Sox1 in red.
Credit
University of Zurich
Journal
Nature Communications
Method of Research
Experimental study
Subject of Research
Animals
Article Title
eural xenografts contribute to long-term recovery in stroke via molecular graft-host crosstalk
Article Publication Date
16-Sep-2025
Stem cell transplant for stroke leads to brain cell growth and functional recovery in mice
Insights about brain cell damage after stroke and repair after transplant could pave the way for therapies that extend the treatment window, as revealed in a lab study led by the Keck School of Medicine of USC.
When someone has a stroke — a leading worldwide cause of death and disability — time is of the essence. Almost nine out of 10 cases are ischemic strokes, caused by restricted blood flow in the brain, and the current gold-standard treatment that breaks up blood clots must be delivered within four and a half hours of symptoms appearing.
Researchers are on the hunt for ways to extend that ticking clock and enable better stroke recovery. One promising prospect is an experimental stem cell therapy to help repair damaged brain tissue, co-developed by scientists at the Keck School of Medicine of USC, the University of Zurich and ETH Zurich in Switzerland. A study in the journal Nature Communications showed that a stem cell transplant performed one week after an ischemic stroke in mice led to recovery.
“There are a lot of patients who cannot get the acute treatment, and their blood vessels remain blocked,” said co-corresponding author Ruslan Rust, PhD, assistant professor of research physiology and neuroscience at the Keck School of Medicine. “If we can bring this treatment to the clinic in the future, it may help patients who have long-term symptoms or large strokes see recovery.”
Employing stem cells to heal damaged brain tissue
Rust and his colleagues reprogrammed human blood cells into neural stem cells — which can mature into neurons — and transplanted them into the damaged brain tissue of mice that had strokes. After five weeks, the researchers compared their recovery to a group of mice from the same litter that had strokes but underwent surgery without transplantation.
The brains of the mice that received transplanted neural stem cells showed more robust signs of recovery than those of untreated mice. The transplant recipients’ brains had less inflammation, more growth of neurons and blood vessels, and more connectivity among neurons than the brains of the mice that did not receive transplanted cells. The treated mice also had less leakage from the blood-brain barrier, which is important for normal brain function and acts as a filter to keep harmful substances out of the brain.
To measure function, the researchers used artificial intelligence to closely track the movement of the animals’ limbs while walking and climbing up a ladder with irregular rungs.
“Recovery can be hard to determine in mice, so we needed to see these little differences,” Rust said. “The unbiased view we got through this deep learning tool gave us a lot more detail about this complex process.”
The team found that treated mice fully recovered the fine motor skills tested in the climbing task five weeks after the transplants. By the end of the study, their gait also improved significantly compared to mice that received a sham surgery.
Clues among the new brain cells that develop
When the researchers looked at which types of cells died off due to stroke, they found roughly a 50% reduction in neurons that secrete gamma-aminobutyric acid (GABA), which decreases activity in the brain cells to which it binds. These GABA-secreting neurons, known as GABAergic neurons, have previously been shown to assist stroke recovery.
The team also explored the fate of the transplanted stem cells, finding that the majority had become GABAergic neurons. This is a possible indication that the local environment where the stroke injured the brain may help steer the development of the neural stem cells.
Rust and his colleagues also analyzed the interactions between the transplanted cells and other cells in the brains of the mice. They found strong activity in several signaling pathways that were shown in prior studies to be associated with regenerating neurons, forming connections between neurons, and guiding how neurons branch out.
“Mechanistic insight can be quite important if we seek to inform new therapies or improve emerging ones,” Rust said. “Understanding the mechanisms allows us to think about adapting a drug that regulates them — perhaps one that’s already clinically approved for a different disease. It could open up a whole new wave of therapies.”
The team is currently investigating other ways to increase activity in the pathways identified in the study and evaluating the results of the transplant in mice for periods longer than five weeks.
“If we can help people by transplanting stem cells into a human stroke patient, we want the cells to be there for the rest of their life,” Rust said. “So our aim would be to look across the whole lifetime of a mouse and see what happens with the cells, and also see whether this recovery is sustained or even improves.”
About this study
The study’s first author is Rebecca Weber of the University of Zurich and ETH Zurich. The co-corresponding author is Christian Tackenberg of the University of Zurich and ETH Zurich. Other co-authors are Beatriz Achón Buil, Nora Rentsch, Patrick Perron, Stefanie Halliday, Chantal Bodenmann, Kathrin Zürcher, Daniela Uhr, Debora Meier, Siri Peter, Melanie Generali of the University of Zurich and ETH Zurich; Allison Bosworth, Mingzi Zhang and Kassandra Kisler of the Keck School of Medicine; Shuo Lin and Markus Rüegg of the University of Basel in Switzerland; and Roger Nitsch of Neurimmune, a Swiss biopharmaceutical company.
The study received support from the Swiss 3R Competence Center; the Swiss National Science Foundation; the Neuroscience Center Zurich at the University of Zurich and ETH Zurich; and the Maxi Foundation.
Journal
Nature Communications
Method of Research
Experimental study
Subject of Research
Animals
Article Title
Neural xenografts contribute to long-term recovery in stroke via molecular graft-host crosstalk
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