Is it possible to regenerate the brain with stem cells after a stroke?

Barcelona"Time is brain," neurologists often say about the need to act as quickly as possible in the event of a stroke. To save the patient's life. To minimize their risk of suffering aftereffects that could cause neurological and motor disabilities, such as speech problems or paralysis. When a stroke interrupts blood flow to the brain—almost always unpredictably—it ravages brain connections like a wildfire, impeding the nutrition of neuronal cells, which ultimately die. Every minute that passes, the affected person loses approximately 2 million neurons and 14,000 neuronal connections. Stroke causes irreversible damage to the affected tissue, and currently there are no therapies to repair it. But what would happen if it were possible to specifically treat the damaged area and restore its function? An international group of researchers has achieved this with a pioneering method: a stem cell transplant.

Scientists from the Keck School of Medicine at the University of Southern California (USC), the University of Zurich (UZH) and ETH Zurich (both in Switzerland) have tested an experimental therapy based on the transplantation of yPS stem cells (or stem cells created in the laboratory from adult cells that are genetically reprogrammed to recover characteristics typical of embryonic stem cells). In an article published this Tuesday in the journal Nature Communications, the researchers They describe how they generated these neuronal stem cells (which can mature into neurons) and transplanted them into the damaged brain tissue of mice, in which they induced a permanent stroke.

After five weeks, the scientists were able to compare the recovery of these mammals with a group of mice from the same litter, also with stroke after-effects, but who underwent surgery rather than a transplant, and they were able to confirm that brain tissue can be regenerated during this period. In fact, they highlight that most of the stem cells transformed into neurons, and even communicated with existing brain cells. "The treated mice also had fewer leaks 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," they explain. Furthermore, they confirmed that the mice had significantly recovered fine motor skills after their walking and climbing abilities were assessed.

New neurons and new connections

Nearly nine out of ten strokes are ischemic, meaning they are caused by restricted blood flow in the brain. The current standard of care, which breaks up blood clots, must be administered within four and a half hours of the onset of symptoms. "There are many patients who cannot receive acute treatment, and their blood vessels remain blocked," explains Ruslan Rust, assistant professor of research physiology and neuroscience at the Keck School of Medicine and co-author of the study. "It is essential to look for new therapeutic approaches for potential brain regeneration after illnesses or accidents," agrees Christian Tackenberg, head scientist of the neurodegeneration group division at the Institute of Regenerative Medicine at UZH. And with this study, the international team has demonstrated that neural stem cells not only form new neurons, but are also capable of inducing regeneration processes.

Joan Vidal, a rehabilitation doctor at the Institut Guttmann – who did not participate in the research – assures that this line of research based on stem cell transplantation is "one of the most promising" that exists for neurological and spinal cord diseases, along with stimulation and neuromodulation. led in Europe by the research centers in Lausanne (Switzerland)In the case of stem cells, the Catalan expert emphasizes that in an animal model such as rats, five weeks is considered a sufficiently significant period, which is why he describes the conclusions as "spectacular." "They are very good, both in the tissues, in the most microscopic studies, and in the entire process of improving inflammation: there is better growth of neurons and vessels, more connectivity... These researchers have extended the animals' lives and there have been observable functional changes," he summarizes.

Another new discovery was that stem cell transplants work better when not performed immediately after a stroke but a week later, as verified by the second study. "The chronic subacute phase is surely the one that interests us most, because it will serve to treat the after-effects of those patients who have been left with lifelong after-effects. Here, cell therapy can restore all this blood circulation and regenerate tissue so that later, with a long rehabilitation process, the patient can recover."

A continued essay

The collaborative team is currently investigating other ways to increase activity in the pathways identified in the study and evaluating transplant outcomes in mice for periods exceeding 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. That's why our goal would be to observe a mouse's entire lifespan and see what happens to the cells, as well as see if this recovery is maintained or even improved," Rust concludes.

Vidal, while urging caution because the cell therapy described this Tuesday is still far from safe and usable in humans, believes that this contribution "is key" to developing preclinical studies that pave the way before it can be tested in people. "The great contribution this group makes to us is the reprogramming of neurons so they can grow and regenerate the affected tissue. I'm convinced it will serve as a basis for doing the same with people in the future," concludes the doctor, who points out that there are nearly 14,000 strokes in Catalonia each year.