*The article was written by researchers Daniel Tornero Brito, Alba Ortega Gasco, and Santiago Ramos Bartolomé, all from the University of Barcelona, and published on The Conversation Brasil platform.
Every year, millions of people see their lives change in a matter of minutes. A blood vessel carrying blood to the brain becomes blocked, neurons begin to die and time runs out. Stroke is one of the leading causes of disability in adults. It is estimated that one in six people will experience one of these accidents, also called a cerebrovascular accident (CVA), in their lifetime.
The human brain is, by far, the most complex organ in our body. Their cellular structure and organization into neural networks allow for complex functions such as language, memory, or abstract decision making. But this same complexity comes at a cost: brain tissue has a very limited capacity for regeneration. Unlike the skin or liver, nerve cells that die are rarely replaced.
Therefore, brain injuries are the cause of many diseases associated with aging, the most serious and common of which is stroke, resulting from an interruption of blood flow in an area of the brain. Although advances in emergency treatments have improved survival rates, there is currently no treatment capable of repairing neuronal damage resulting from stroke.
Rehabilitation helps restore some function, but in many cases patients suffer from permanent motor and cognitive limitations. Moreover, after a stroke, the risk of developing depression, dementia, and other neurological diseases increases. But this may soon change, thanks to the development of stem cell-based treatments.
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A new therapeutic horizon
In recent decades, cell therapies have opened the door to a new generation of treatments in regenerative medicine. These treatments seek to replace or repair damaged tissue, introducing new cells capable of surviving, maturing and eventually performing the functions that were lost.
As previously mentioned, this is especially important in diseases affecting the brain. Despite its high potential, its development is slow, as it must adapt to the legislation in force in each region and depend on large financial investments.
A crucial precedent occurred in the late 1980s at Lund University Hospital in Sweden. A team led by Anders Björklund and Ol Lindvall were able to transplant neural stem cells into the brains of patients with Parkinson’s disease. This neurodegenerative disease is characterized by the gradual loss of dopaminergic neurons, which are necessary for controlling body movements.
The results were extraordinary: by replacing damaged nerve cells, many patients regained motor function for more than a decade. These experiments were the first solid evidence that the human brain could be repaired using living cells.
Since then, research has advanced, techniques have been improved and European regulations have established stringent frameworks to ensure the safety and quality of these treatments, which are now included in the Advanced Therapy Medicines (ATMP) category.
Currently, various clinical trials are being conducted around the world that continue the work of Bjorklund and Lindvall and which bring hope to patients suffering from Parkinson’s disease and many other diseases that affect our brain.
Stroke challenge
Although this story has inspired countless studies, stroke presents a different challenge than Parkinson’s disease. Ischemic injury tends to be more extensive and heterogeneous: it affects not just one type of cell, but several groups of neurons, glial cells and also blood vessels.
Moreover, after the transplant, it is not enough for the cells to survive in the patient’s brain. They must integrate functionally, that is, transmit their axons (the extensions that transmit nerve impulses) and establish synapses or appropriate connections with surviving neurons, to become part of the brain’s circuitry.
It’s like trying to reconstruct not only the structure of the bridge, but also its traffic: connections have to be set up in the right way for information to flow. So, in addition to adding new cells, the challenge of a stroke is to rewire the brain.
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A stroke, also known as an ischemic stroke or ischemic stroke, is an interruption of blood flow to an area of the brain.
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The accident can happen for several reasons, such as the buildup of fatty plaques or the formation of a clot – causing a stroke – bleeding due to high blood pressure and even the rupture of an aneurysm – causing a hemorrhagic stroke.
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There are many common symptoms in ischemic and hemorrhagic strokes, such as: very severe headache, weakness or numbness in some parts of the body, paralysis and sudden loss of speech.
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There is no cure for stroke, but it can be prevented in most cases. When this happens, it is possible to invest in treatments to improve the condition and in rehabilitation to reduce the risk of consequences.
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Most often, it occurs in people over 50 years of age, however, it can also affect younger people. The disease can occur as a result of five main reasons
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Smoking and malnutrition: It is important to follow a healthy diet rich in vegetables, fruits, and lean meat, in addition to practicing physical activity at least 3 times a week and not smoking.
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High blood pressure, cholesterol, and diabetes: These diseases must be adequately controlled, in addition to following healthy lifestyle habits to reduce their negative effects on the body, because they can lead to stroke.
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Heart or blood vessel defects: These changes can be detected in routine consultations, and should be monitored if identified. Some people may need to use medications, such as anticoagulants.
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Illegal drugs: It is recommended to seek help from one of the centers specialized in drugs in order for the detoxification process to take place and thus improve the patient’s quality of life, which reduces the chances of stroke.
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Increased blood clotting: diseases such as lupus, sickle cell anemia or thrombophilia. Diseases that lead to inflammation of blood vessels, such as vasculitis. Or brain spasms that impede blood flow
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Genetic engineering as a turning point
This is where genetic engineering comes into play, one of the most transformative technologies in modern biology. This system allows cells to be modified to make them more effective, more resistant or better able to integrate into damaged tissue.
In our case, we incorporated the gene that encodes the protein BDNF into cultured cells (Brain-derived neurotrophic factor), a neurotrophic factor that is involved in brain development and promotes the growth of axons and the formation of synapses. In doing so, we seek to facilitate the functional integration of new neurons into the injured brain, an essential step so that the transplant not only bridges the gap but restores neural connectivity.
Discussion is necessary
But this ability to manipulate genes also raises ethical dilemmas, especially regarding the limits of its application and potential long-term effects. For example, the first organ transplants in the Parkinson’s patients mentioned above were performed using stem cells from fetal tissue.
Today, thanks to the work of Japanese researcher Shinya Yamanaka, who won the Nobel Prize in Medicine in 2012, and his discovery of induced pluripotent stem (iPS) cells, it has become possible to generate stem cells from a patient’s own adult cells. Therefore, it is very common today to generate these induced pluripotent stem cells in vitro from skin biopsies.
This avoids most of the ethical conflicts related to the use of embryos and reduces the risk of immunological rejection. Therefore, the question is no longer whether we can modify cells to repair the brain, but by what standards, under what regulation and with what responsibility.
The history of medicine is made up of small victories in the face of the impossible. Just a few decades ago, the idea of healing a damaged brain seemed like a far-fetched dream. Today, thanks to the combination of biology, genetic engineering, and regenerative medicine, this dream is taking shape in laboratories. There are still many challenges to solve, but each new advance reminds us of something fundamental: the brain can not only learn, but it can repair.
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