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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.”

Christian Tackenberg, the Scientific Head of Division in the Neurodegeneration Group, 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.”

An estimated 7.2 million Americans over age 65 currently live with Alzheimer’s disease (AD). That number is expected to nearly double to 13.8 million by 2060. These increases reflect more than demographic shifts; they point to a growing public health crisis that requires a new, proactive approach. While chronological age is the strongest known risk factor for cognitive decline, losing cognitive function is not an inevitable part of aging.

As AD and other forms of cognitive decline continue to rise at an alarming rate, researchers from Florida Atlantic University’s Charles E. Schmidt College of Medicine, highlight a powerful and untapped path to prevention. 

In a commentary published in The American Journal of Medicine, the researchers urge clinicians, public health professionals and policymakers to implement coordinated efforts to support lifestyle-based interventions that can help reduce the growing burden of cognitive decline in the United States and worldwide.

“While deaths from cardiovascular disease have declined since 2000, deaths from Alzheimer’s disease have surged by more than 140%,” said Charles H. Hennekens, M.D., FACPM, FACC, co-author, the First Sir Richard Doll Professor of Medicine and Preventive Medicine, and senior academic advisor, Schmidt College of Medicine. “At the same time, it is estimated that up to 45% of dementia risk could be attributed to modifiable lifestyle and environmental factors.”

Lifestyle risk factors like physical inactivity, poor diet, obesity, alcohol use, and conditions such as hypertension, diabetes, depression, and social or intellectual isolation are believed to contribute to cognitive decline. The authors point out that the same therapeutic lifestyle changes proven effective for reducing risks of cardiovascular and other major diseases may also help reduce cognitive decline – potentially with additive effects when multiple risk factors are present.

The commentary highlights the recently published results from POINTER, the first large-scale U.S-based randomized trial to test whether intensive lifestyle changes can improve cognitive outcomes in older adults at high risk of decline. In this trial, participants who were assigned at random to a structured, team-based lifestyle intervention showed statistically significant and clinically meaningful improvements in global cognition over two years. These gains were especially notable in executive functions such as memory, attention, planning and decision-making. The intervention emphasized regular physical activity, a combination of Mediterranean and DASH-style diets, cognitive stimulation and social engagement – reinforced through ongoing professional guidance and group support.

These findings are similar to an earlier Finnish trial, the FINGER trial, in which participants with elevated cardiovascular risk scores assigned at random to a multidomain lifestyle approach experienced cognitive benefits.

“The data from both these landmark, large scale randomized trials demonstrate that lifestyle changes – previously shown to reduce heart disease and cancer – also hold transformative potential for brain health,” Hennekens said.

The researchers also speculated about biological mechanisms that may underlie these benefits. Physical activity, for example, increases brain-derived neurotrophic factor, which supports hippocampal growth, while also improving blood flow and reducing inflammation. Healthy dietary patterns like the Mediterranean and DASH diets can lower oxidative stress and improve insulin sensitivity as well as risks of cardiovascular disease. Quitting smoking may help preserve brain structure and white matter integrity, and regular social and cognitive engagement promotes neuroplasticity and mental resilience.

“The implications for clinical practice, public health and government policy are potentially enormous,” said Parvathi Perumareddi, D.O., co-author and an associate professor of family medicine in the Schmidt College of Medicine. “Clinicians now have powerful, evidence-based tools to help their patients prevent or slow cognitive decline – tools that go beyond medications, are generally low-risk, and are cost-effective. Public health agencies could adopt the framework of trials like POINTER and FINGER to develop brain health programs.”

On the policy front, the researchers note that potential cost savings are large, particularly when considering the high price and limited effectiveness of many new pharmacologic agents, which may cause common and less serious side effects like nausea, headache and fatigue, as well as more rare but more serious risks like confusion or gastrointestinal bleeding. Modeling studies suggest that reducing key risk factors by even 10% to 20% each decade could lower the burden of cognitive decline by up to 15%.

Beyond the health care system, the societal costs of dementia are staggering. In 2024, nearly 12 million family members and unpaid caregivers provided an estimated 19.2 billion hours of care to individuals living with dementia – amounting to a societal cost of more than $413 billion. Caregiving also takes an emotional toll, often resulting in mental health challenges and caregiver burnout. The researchers emphasize that these realities underscore the need for practical, community-based solutions that support both patients and caregivers and reduce the long-term burden on families and the economy.

“While more research is needed, the current totality of evidence supports a clear path forward: invest in lifestyle-based strategies to protect brain health,” said Hennekens. “Doing so will not only benefit individuals at risk but also serve as a powerful tool for reducing national and global health care burdens related to cognitive decline.”

Reference: Dunn J, Perumareddi P, Hennekens CH. Prospects for clinicians to reduce cognitive decline in elderly patients. Am J Med. 2025:S0002934325005765. doi: 10.1016/j.amjmed.2025.08.042

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