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Cells with a thousand faces

Brazilian teams use cell therapy to treat experimentally autoimmune diseases and lesions in the brain

In Brazil, it is not just the sufferers from heart problems who enjoy the benefits – still at an experimental stage – of adult stem cells, the object of intense interest, because they are capable of differentiating themselves from the cells of some tissues of the body, like those of the heart and of the brain. After the pioneer experiments of Alberto Marmont, of the Hospital San Martino, in Génova, Italy, and of Alan Tyndall, of Basel, Switzerland, the use of this kind of stem cells is getting another application: in the treatment of the so-called autoimmune diseases, when the immune system attacks healthy tissues and organs of its own organism.

Since 1996, when Marmont and Tyndall announced the conclusions of their tests with human beings, the experiments with stem cells has spread through European, American and Brazilian centers. At the Ribeirão Preto School of Medicine, of the University of São Paulo (USP), Júlio César Voltarelli concluded nine transplants of stem cells for treating autoimmune diseases, carried out in collaboration with doctors from two hospitals in São Paulo, the Albert Einstein and the Syrio-Lebanese, and one from Belo Horizonte, the Socor.

According to an article to be published shortly in Bone Marrow Transplantation, four patients were suffering from erythematous systemic lupus, a serious inflammation that affects the skin and the joints, and causes progressive damage to the kidneys. Three others were suffering from multiple sclerosis, in which the defense cells destroy the myelin sheath, a covering that protects the neurons (nerve cells) and leads to progressive physical incapacity. Another patient was suffering from systemic sclerosis, a disease that causes the loss of elasticity in the skin and in internal organs, and kills by respiratory insufficiency. Besides systemic sclerosis, the ninth patient had lupus.

In work connected with the Cell Therapy Center, one of the Research, Innovation and Diffusion Centers (Cepids) supported by FAPESP, Voltarelli gave the patients chemotherapy based on medicines called immunosupressors, which eliminate the cells from the immune system. At the same time, he applied doses of a hormone that stimulates the stem cells to migrate from the bone marrow – where they are concentrated – to the blood, which was filtered to separate the stem cells from the others. After a higher dose of immunosupressors, the researcher put the stem cells back in the patients’ blood.

Voltarelli believes that the stem cells replace the blood cells and thus help to restore the immune system debilitated by chemotherapy. Of the nine persons treated, three have died – a fact that the doctors attribute to complications caused by the chemotherapy and by the seriousness already being shown by their diseases. The other six improved, although they remain under medical care. Five of them did not need any more medicines to inhibit the immune system, and only one was given one more dose of immunosupressors. “Little by little, we are making headway”, says Voltarelli, who is part of the team that is preparing the first studies of two other problems for human health, rheumatoid arthritis and diabetes.

Damaged neurons
In another series of experiments, Rosalia Mendez Otero and Gabriel de Freitas, from the Federal University of Rio de Janeiro (UFRJ), and Maria Lucia Mendonça, from the Pro-Cardiac Hospital managed to reduce – for the time being, only in rats – the damage arising from the death of part of the brain for lack of oxygen and nutrients. Known as an ischemic stroke or cerebrovascular accident (CVA), this problem can lead to the immobility of arms and legs, and even to the loss of speech. Deprived of blood, the neurons die and release glutamate, a chemical substance that carries out the communication between the nerve cells. In high concentrations, though, the glutamate becomes toxic and kills the neighboring cells, extending the damage.

Rosalia noted that, when she injected stem cells into the blood of rats with cerebral ischemia, these cells make their way to the damaged area, where they install themselves and allow the neurons around the damaged area to recuperate – seemingly by releasing chemical substances that counterbalance the action of the glutamate. Should future research confirm this result, the use of stem cells may become an effective form of preventing, or at least lessening, the secondary effects, which only appear a few days after cerebral ischemia. The medicines available nowadays dissolve the clot that blocks the flow of the blood, but only reduce the damage if taken in the first three hours after the ischemia. The intention with the stem cells is to extend the period in which it is still possible to reduce the damage created by the lack of irrigation of the brain.