Stroke, how modified stem cells could one day repair the brain

Stroke, how modified stem cells could one day repair the brain
After an ischemic stroke, the brain regenerates very little, leaving millions of survivors with lasting after-effects. European researchers are now exploring a new avenue combining stem cells and genetic engineering to reconnect damaged brain circuits.

A blood vessel becomes blocked, oxygen no longer reaches the brain, and within minutes millions of neurons die. Every year, stroke affects millions of people, approximately one in six during their lifetime, and in Europe it is among the leading causes of death while remaining the leading cause of disability in adults.

The problem is brutal: brain tissue regenerates very little, unlike the skin or the liver, and no current therapy can recreate the destroyed neurons. However, the combination between
regenerative medicinestem cells and genetic engineering are beginning to outline a scenario long considered impossible. How could these reprogrammed cells, one day, repair a brain after an ischemic stroke?

Professors Daniel Tornero Prieto, Alba Ortagea Gasco and Santiago Ramos Bartolomé from the University of Barcelona, ​​describe this new therapeutic horizon in The Conversation.

Why the brain repairs so poorly after an ischemic stroke

In a
ischemic strokea clot blocks a cerebral artery, depriving an area of ​​blood and oxygen. Neurons die, but also glial cells and vessel cells. The thrombolysis treatment window is limited to a few hours after symptoms, which leaves a majority of patients without a solution for the repair phase.

The consequences are seen on a daily basis: paralysis of one side of the body, problems with language, memory, attention, with an increased risk of depression and dementia. Around a third of patients recover relatively well, almost 40% have after-effects requiring regular help and barely 10% return to almost normal functioning.

Stem cells and genetic engineering to reconnect brain circuits

In the late 1980s, a Swedish team transplanted neuronal stem cells into people with Parkinson’s disease. By replacing the dopaminergic neurons destroyed, several patients regained motor function for more than ten years. This experiment showed that the human brain could be repaired using living cells.

Stroke, however, poses a larger challenge: it’s not just about adding neurons, but rebuilding entire circuits. Researchers therefore modify genetically modified stem cells so that they produce more BDNF, the BDNF (Brain-Derived Neurotrophic Factor), a protein that supports brain development, axon growth and synapse formation. The idea is that these cells don’t just fill the hole left by the injury, but wire properly with the surviving neurons.

Personalized iPS cells for future post-stroke therapy

The first neuronal transplants were based on fetal tissue, a source of lively ethical debates. The discovery of
iPS cells by Shinya Yamanaka has changed the situation: by reprogramming adult cells, for example from a skin biopsy, into pluripotent stem cells, it becomes possible to manufacture tailor-made neurons for each patient. These cells can then be transformed into neural stem cells and then engineered to express BDNF before targeted injection into the injured area.

It remains to ensure that these cells do not transform into tumors, that they do not carry dangerous mutations and that they integrate sustainably. In Europe, these approaches fall into the category of innovative therapy productssubject to very strict quality and safety controls. Teams are also testing hydrogels based on hyaluronic acid, capable of serving as support for transplanted cells and guiding their growth in the brain. For the moment, everything is still being decided in the laboratory or in very early trials, but for stroke survivors, this avenue is already opening up a radically new perspective.