A study from the University of Zurich found that mice with stroke damage regained their sense of motion after human stem cells were placed into their brains. The therapy also helped repair the brain’s protective barrier, lowered inflammation, and improved blood vessels.
The study, under the guidance of Christian Tackenberg, Scientific Head of the Neurodegeneration Group at the University of Zurich’s Institute for Regenerative Medicine, and postdoctoral researcher Rebecca Weber, demonstrates that neural stem cells are capable of more than merely replacing lost neurons. The cells activate a wide-ranging healing response throughout the brain.
Stem Cells as a Regenerative Tool
About one in four adults will have a stroke at some point in their life, making it extremely common. Roughly half of those who survive a stroke are left with lasting problems, such as paralysis or difficulty speaking.
The injury results from a stroke that either denies oxygen to portions of the brain or produces bleeding that kills brain cells. Because no treatments can rebuild the lost tissue, the damage has been regarded as permanent once those cells are gone.
Tackenberg and his team examined the idea that neural stem cells can develop into several kinds of nervous system cells. The researchers used human neural stem cells derived from induced pluripotent stem cells — ordinary human body cells that have been reprogrammed to renew their power to develop into many different cell types.
The team conducted two studies in partnership with a group led by Ruslan Rust from the University of Southern California, during which they brought about lasting strokes in mice. The brain injury was constructed to closely mirror significant features of stroke in humans. Since the cells being transplanted were of human origin, the mice were genetically modified so that their immune systems would not reject them.
The Stem Cells Survived and Made Neurons
Seven days after the strokes were induced, the researchers put the neural stem cells into the injured parts of the brain. The team followed what happened in those damaged regions using imaging techniques and biochemical analyses over a five-week period.
In this exchange, “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,” is what Tackenberg says.
Making new neurons alone won’t bring back functional gains. The key is getting those fresh cells to hook up with existing neural networks.
The Whole Brain Responds
Investigators discovered that the treatment set off a far-reaching healing reaction, in which new blood vessels grew inside the injured brain tissue, inflammatory responses subsided, and the barrier between blood and brain regained its strength.
This protective boundary separates circulating blood from brain tissue and controls what crosses through it. When it is damaged after a stroke, inflammation and further injury can result.
“Our analysis goes far beyond the scope of other studies, which focused on the immediate effects right after transplantation,” Tackenberg explains.
The most significant result was that the biological changes translated into better mobility for the animals. The stem cell transplants corrected the motor problems caused by the strokes in the mice, and that improvement was gauged in part by AI-assisted analysis of their gait.
Timing and Production
The scientists planned their experiments with eventual human treatment in mind. One example of this approach is that the stem cells were produced without any reagents derived from animals. This matters when developing therapies for people, because avoiding animal-derived materials may reduce potential safety and regulatory complications.
The CiRA at Kyoto University worked together with the University of Zurich team to develop a set production plan.
The second study offered an important insight into timing, with the researchers discovering that stem cell transplantation was more effective when carried out one week after a stroke rather than right away.
The added time means the method would be simpler to put into practice in a doctor’s office. Medical staff would be able to get ready before the treatment needs to be given, rather than having to give it right away during the period following a stroke.
Before the Therapy is Tested Widely
While the results are promising, the researchers caution that several barriers must still be overcome before the therapy can be tested widely in people.
“We need to minimize risks and simplify a potential application in humans,” he says.
There is worry about unchecked development of stem cells within the brain. Tackenberg’s team, once again collaborating with Ruslan Rust, is building a kind of safety switch designed to stop that from taking place.
The team is also searching for a gentler method of delivering the cells. Rather than transplanting stem cells directly into the brain, they want a route that would need less surgery.
The study holds out promise that a similar method might one day assist in restoring functioning in the human brain after a stroke.
What the Study Measured
The Zurich team’s approach sets itself apart from earlier work. Where past studies have concentrated on the immediate effects following transplantation, this study followed the cells across five weeks and measured several outcomes.
- Blood vessels forming in damaged brain tissue
- Inflammatory processes becoming less intense
- The integrity of the blood-brain barrier improving
The study draws on human neural stem cells, a detail that raises the potential for eventual human trials. By working with the defined production method developed at CiRA in Kyoto University, the research removes animal-derived reagents, a move that could ease safety and regulatory hurdles for human therapies.
The Scope of the Study
Regenerative therapies for neurological damage are closer thanks to the Zurich team’s work. Their research demonstrates that neural stem cells can regenerate brain tissue, prompt a healing response throughout the brain, and enhance motor function in animals.
The research underscores the significance of timing, noting that transplantation carried out one week after a stroke produced more favorable outcomes than immediate administration of the treatment. This finding may ease the method’s application within a clinical setting.
Before human testing can begin, the Zurich team needs to address safety issues and make the delivery method simpler. The safety switch and less-invasive delivery routes under development by Tackenberg and Rust are steps toward that goal.
Source material: “Stem cells reverse stroke damage and restore movement in mice,” ScienceDaily.
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