Stroke treatment: Cellular technologies in the cell of the law

Immunology for the brain

Yulia Moiseeva, "Honest Word" No. 42-2013

The Novosibirsk Institute of Clinical Immunology has found a way to effectively rehabilitate stroke patients. The world's first development involving the use of immune system cells will be used in the treatment. Despite the difficulties associated with the adoption of the law on cellular technologies in our country, scientists are testing the methodology step by step and hope that sooner or later the innovation will enter clinical practice

The consequences of a vascular catastrophe – as doctors often call acute cerebrovascular accident or simply stroke – remain one of the main causes of disability worldwide. Unfortunately, a blow to the patient's nervous system often becomes fatal, and the rescued patients, as a rule, remain without guarantees for further full-fledged life.

Proven: safe

The Novosibirsk Institute of Clinical Immunology started studying stem and immune cells twenty years ago. Back then, at the dawn of Siberian research, no one thought that very soon cellular technologies would become a new direction in the treatment of many diseases. In 1995, a clinic was opened at the Institute, which gave scientists the opportunity to test their developments in practice. One of the key departments of the clinic was the bone marrow transplantation department – the first and currently the only one outside the Urals. The practical implementation of hematopoietic stem cell transplantation technology, which has already become the standard for the treatment of blood tumor diseases abroad, has unfolded here. Having already had serious experience working with stem cells, the institute's staff succumbed to the temptation to expand the scope of their application. By that time, it became known that stem cells can take part in regeneration processes, and also that the axiom about the inability of nervous tissue to recover is erroneous. Then the idea came up to activate the repair processes in the central nervous system with the help of stem cells, that is, to restore the impaired functions of the nervous system with the help of cellular technologies.

The breakthrough idea has visited the minds of many scientists around the world, and already today in Russia and abroad, developments are underway in the field of restoring the nervous system, including after a stroke, using cellular technologies. Why cells? The fact is that stem cells retain their viability for a long time, and also have the ability to produce so–called neurotrophic factors - special proteins that are responsible for the survival and "nutrition" of neurons.

Moreover, Siberian immunologists have suggested that a very similar range of factors can be produced by immune cells, in particular by such a type as macrophages. Therefore, to restore the nervous system, they decided to use not only stem cells, but also cells of the immune system. It turned out that macrophages play an extremely important role in the restoration of damaged tissue. Moreover, a special population of so-called M2 macrophages has the ability to stimulate reparative processes. To obtain these cells from the blood, scientists have developed an original technology.

Now the staff of the Institute of Clinical Immunology is embarking on the second stage of clinical trials of the method. There are already results proving its effectiveness. However, according to the developers, this is not the main thing. The main thing at the first stage is that the method has demonstrated its safety. And this means that we can safely continue further, perhaps more daring, research.

– Six months after cell therapy, we saw a statistically significant decrease in neurological disorders, – says Elena Chernykh, Deputy Director for Research and head of the Laboratory of Cell Immunotherapy at the Institute of Clinical Immunology of the SB RAMS. – The greatest effect was observed in the group of patients in whom the cells were injected before the expiration of twelve months after the stroke.

The patients' motor functions improved, speech disorders decreased, and the possibility of self-service increased. A pronounced clinical effect, defined as a reduction in stroke severity by four or more points on a special stroke severity scale, was observed in 43 percent of patients. But the most important conclusion that we have made, and, in fact, for the sake of which we started clinical trials, is that it is completely safe. We did not see any complications associated with the introduction of cells, or any adverse effects.

Until now, the only type of stroke treatment with proven effectiveness remained thrombolysis – the dissolution of a blood clot, which causes a violation of cerebral circulation. However, only a third of patients respond well to this therapy.

Moreover, due to the fact that the method can be used only in the first three to four hours after an acute violation of cerebral circulation, this type of therapy is available only to three to four percent of patients. As for spontaneous, that is, self-recovery of damaged nervous tissue, in severe stroke, effective recovery is observed only in half of patients.

During clinical trials, patients were divided into two groups. The first group included patients who had suffered a stroke less than a year ago, the second group consisted of those who had more than twelve months since the brain hemorrhage. The results of the study of both groups showed that the earlier cell therapy is carried out, the more effective it is. Now scientists are going to start studying a new group of patients who have had very little time since the stroke.

– We already have certainty about the time of cell injection: it seems that the most reasonable time for such therapy should be no more than three to six months from the moment of stroke, – says Elena Chernykh. – In the future, we need to determine the optimal dose of injected cells and, maybe, we will work on a therapy that combines different types of cells. Today, approaches to the treatment of stroke patients are being actively sought all over the world with the help of cell therapy. Of all the options available today, this is the direction that inspires both clinicians and experimenters the most, because there are already preliminary positive results. If we are now moving to the second phase of clinical trials, then the second phase is already underway abroad, and I think they will soon begin the third, final one there.

The cells of the body and the cell of the law

It is worth noting that previously, in order to restore brain activity, immune cells were not used anywhere and by anyone. However, it is still problematic to introduce vital treatment: the law regulating the use of cellular technologies in Russia is still under development, and neuropathologists do not risk conducting clinical trials at the early stages of the disease.

– In the countries of Europe and America, the regulations for the development and use of cell technologies based on stem cells are legally prescribed, and it would seem that we already have the experience of other countries, – says Elena Chernykh. – For some reason, they still can't accept the law on cellular technologies in our country. But if we don't move forward, we will never be able to understand whether we are acting wrongly or not. We are looking for, and from what we find, we choose the best – this is a normal scientific path of development. It remains to be hoped that something will change someday. Surprisingly, despite all the conservatism, scientists and clinicians from Europe and the USA recently held two major scientific forums under such a bold name as "Cell therapy as a new paradigm in the treatment of stroke." These conferences brought together a huge number of participants from different fields of science and different countries. It already means something. And in our country, these studies are practically not supported.

– Our research has shown that rehabilitation should be started as early as possible, and the introduction of cells can already be considered the beginning of rehabilitation, – continues Natalia Starostina, Deputy Director for Therapeutic Work at the Institute of Clinical Immunology of the SB RAMS. – That is why we switched to clinical trials of the technology in patients at the earliest stages after a stroke. The best option would be the introduction of cells a week after the onset of the disease, while cell sampling should be done in the first hours after the onset of the disease. But, unfortunately, clinicians are afraid to take blood in the first hours after a stroke. They don 't agree even for three months…

The less we know, the scarier, scientists and doctors are sure. And this applies not only to those who become the object of medical innovations, but also to the development doctors themselves. Apparently, that's why there are so many conjectures and myths around stem cell treatment. For the first time, the world has learned everything about cellular technologies

20-30 years ago, when hematopoietic stem cell transplantation became the standard method of treating malignant blood diseases. Even by the standards of today's pace of technological progress, this period is quite short. Therefore, it is not surprising that many (and not always far from medicine) people do not distinguish between completely different types of stem cells.

So, embryonic cells are really not suitable for the treatment of the human body. Transplantation of such cells to animals leads to the development of tumors. However, organs and tissues grown from such cells may find use in the future. But an adult's own stem cells, and even more so immune cells, do not cause the development of tumors. These cells constantly circulate in the body, and when damaged, they intensively enter the blood from the bone marrow. This is exactly the type of cells that take part in the regenerating processes of the body. Their isolation by artificial means and subsequent administration only stimulates the natural recovery of affected cells.

Some types of cells, despite their high reparative potential, can suppress immunity in high doses. Therefore, before carrying out cell therapy, patients should be carefully examined for the presence of oncological diseases.

– Stem blood cells come from the bone marrow into the blood and come back, this is a physiological process, – explains Elena Chernykh. – If something happens in the body, such as a heart attack, stroke or injury, the process of mobilization of stem cells occurs: they are released in larger quantities from the bone marrow into circulation. For what? Most likely, in order to replenish the reparative, or restoring reserves of the body. This mechanism was laid down by nature itself. We are only trying to strengthen these processes by isolating and using these cells.

And yet, for most people, cellular technologies are still beyond understandable, and therefore safe. From this point of view, delays in the legislative regulation of the use of stem cells are quite understandable. In the meantime, Siberian scientists hope that by the time the trials of the new method are completely over, cellular technologies will become more accessible to both patients and doctors.

Portal "Eternal youth" http://vechnayamolodost.ru 23.10.2013