Waiting for a miracle

Stem cells: a friend? an enemy? a panacea?

Polina Loseva, "The Attic"

Almost 110 years since the opening. More than 26,000 scientific articles in the last year alone. Hundreds of clinics around the world promise patients healing from any diseases. However, eternal youth for some reason does not come. On the eve of the III National Congress on Regenerative Medicine, which will be held in Moscow on November 15-18, we talk about what is really worth waiting for from stem cells. And we draw your attention to the traps that you should not fall into.

High hopes

A stem cell is a cell that is able to actively divide and produce cells of different types. This simple definition covers all the variety of stem cells currently known. And it is already enough to place on these cells the responsibility for our happy future. Stem cells often resemble innocent children who have everything ahead of them, for whom the future is and whose consciousness is still a blank slate. Who, if not them, can make our world a better place.

It's worth noting here that in some ways stem cells really are a blank slate. It is possible to depict the development of an organism in the form of a tree, which will be based on a zygote. Then each branch divides the cells into groups with a specific fate. Some form the tissues of the embryo, others form the placenta. Then its shoots branch further: some cells give rise to the skin and its derivatives, others to the circulatory system, and others to bones… As a result of many branches, cells of a specific type are obtained: lymphocytes, photoreceptors, fibroblasts, etc. If we go back to the comparison with children, then we can imagine the life path of the school class. First, they all study in the same program and can choose any profession, then they are divided into profiles, then they specialize and finally focus on one specific activity. At the same time, if we take an adult organism, then unlike the embryo of "elementary school students" (i.e. stem cells with great prospects) we won't find it there. Most of the adult stem cells that each of us has with us right now are rather at the university stage and can only give a small list of derivatives.

So, we have a population of cells from which different cell types can be obtained. Naturally, there is a temptation to "plug holes" with their help, that is, to use stem cells to repair damage in the body. They broke the bone – injected stem cells – repaired the bone. Fast and convenient. And, without waiting for the results of clinical trials, one after another clinics appear offering people treatment with "miracle cells". Diseases amenable to such treatment, according to some sites, number in the dozens. Among them, there are even those that are not directly related to cell death (and therefore, in theory, not treatable by the "just add the right cells" method), such as Down syndrome or type 2 diabetes mellitus (insensitivity to insulin). But even for those who were lucky enough to avoid diseases from the list, there are baits in the clinics. If stem cells are like children who still have everything ahead of them, then when they get into the body, they should also make it younger. Therefore, the Internet is replete with offers of procedures for local (cosmetic) and complete rejuvenation of the body. However, how to measure the degree of rejuvenation is also still unknown.

Totipotent cells have the greatest range of possibilities. Only fetal tissues (but not placental tissues) can be obtained from pluripotent (embryonic) ones. In an adult organism, only multipotent cells can be detected (they can give several types of cells) and unipotent cells (they can give only one type).Mike Jones, Wikimedia commons.

Big trouble

What stands in the way of the transformation of stem cells into a panacea and elixir of youth and prevents us from believing such proposals? Imagine an organism in the form of a country in distress, such as an earthquake or tsunami. People (cells) are dying, houses (tissues) and entire cities (organs) are being destroyed. We decide to help this country and send a landing party of middle school students there. We just drop them off from a helicopter (we inject them intravenously) and see what happens to them there. We would like the children to determine for themselves where the trouble is in the country, get to the place and make up for the shortage of labor. Let them, we think, find the hardest-hit city themselves, assess that there are practically no firefighters and confectioners left there, quickly master these professions, learning from the experience of survivors, and get down to business.

However, in fact, this is not always the case. Children can scatter around the country and get lost, then we will not notice any effect. They can master any profession, including those that are not the most necessary. In the worst case, they can, taking advantage of the general anarchy, build themselves a separate city (tumor) and settle there, looting in the surrounding settlements. History can serve as a sad life example here Jim Gass, an American who suffered from partial paralysis due to a stroke. He was treated in clinics in China, Argentina and Mexico, where he was injected not only with adult, but also with embryonic stem cells. The result was a large tumor in the spinal canal, which almost completely paralyzed the patient. At the same time, in the message of researchers interested in this case, it is claimed that the tumor was formed from cells injected into the body, and not from the patient's own tissues. Partially restored mobility was possible only after radiation therapy.

Fortunately, such cases can be avoided if embryonic cells are not introduced into the adult body. As we have already said, adult stem cells have a smaller range of possibilities, so tumors usually do not form from them. However, even careless handling of adult cells can lead to unexpected consequences. So, the magazine Scientific American tells about a woman who was injected with stem cells to "rejuvenate" her face, and the result was a bone formation in her eye. The cells were her own, extracted from adipose tissue. It is known that adipose tissue stem cells can produce various connective tissue derivatives, including cartilage and bones. In addition to cells, cosmetologists often inject non-cellular products under the skin to prevent the formation of wrinkles. One of them – calcium salt – presumably acted on stem cells, directing their development towards the bone. In other words, in this case, a group of schoolchildren successfully mastered the profession of builders and erected a concrete structure right in the middle of an airfield receiving humanitarian aid from other countries.

Great achievements

Stem cell treatment does not always end sadly. If you use them carefully and follow proven protocols, you can achieve serious results. For example, in medicine, bone marrow transplantation (containing hematopoietic stem cells) has long been used to restore hematopoiesis. But blood stem cells are now the only stem cells whose treatment is approved By the U.S. Food and Drug Administration.

Adipose tissue stem cells have not yet learned how to use them directly, but they are known for their anti-inflammatory properties. This may explain the improvement in their treatment of a variety of diseases accompanied by inflammation (neurodegenerative, autoimmune, etc.). And in Canada, a drug of these cells has already been approved to avoid immune conflict during red bone marrow transplantation.

Finally, medicine does not cease to please us with success in restoring epithelial tissues. In a sense, they are the easiest to recreate, because they have an easily reproducible structure (even layers of cells lying on top of each other) and are rich in dividing cells (for regular renewal). So, for the treatment of burns and open wounds, several skin equivalents have been developed, consisting of multiplied patient cells that are selected from the surviving areas. They are at different stages of clinical research, some are sometimes used in practice, but none of them is yet widely used. In Europe, they learned to grow the cornea – the outer transparent shell of the eye, also consisting of even layers of cells, but transparent, unlike the skin. Stem cells are taken from the surviving part of the cornea and cultured in the laboratory, which allows people with severe corneal injuries, such as burns, to save their eyesight. And more recently, we rejoiced at another masterpiece of cell therapy – the restoration of the skin of a boy suffering from epidermolysis bullosa (a congenital genetic disease accompanied by detachment of the skin). Some of his skin stem cells were taken from him, a corrected copy of the gene was injected into them and whole skin layers were grown from them. At the same time, both adult cells and stem cells turned out to be healthy, and there were no more detachments. However, so far this is only a one-time case, and the technology has to be confirmed by clinical studies.

Beware of fakes

Among the cellular technologies that clinics use to treat patients, unfortunately, there are quite a lot of questionable ones. So, in the USA, as we have already written above, only one type of therapy is officially approved – to maintain hematopoiesis. At the same time, as of June 2016, 570 clinics were found in this country advertising a wide variety of stem cell applications. And this phenomenon is not strictly American – there is enough of this, in general, everywhere.

Screenshot of the clinic's website offering stem cell treatment for sheep.

Having armed the reader with knowledge about the current state of regenerative medicine, we would like to finally mention the main traps that await customers in the advertising texts of dubious clinics.

• "Like is treated like." You can find these claims on websites offering treatment with plant stem cells or even Swiss sheep. Probably, the authors mean that the stem cells of different living organisms are similar. Alas, we will have to disappoint them: no research confirms this thesis.

• "Embryonic cells have the highest degree of activity, their transplantation is also carried out to the closest relatives." We have already talked about how such transplants end. At the moment, there is not a single treatment technology using these cells in the American database of world clinical trials.

• Long lists of indications for treatment. Some clinics offer to cure dozens of a wide variety of diseases. Remember that the approved therapy options can be counted on the fingers of one hand.

• "General rejuvenation of the body." It is not very clear what is hidden under these words. Apparently, this is just an appeal to the metaphor of "young cells": the more cells, the younger the body.

• "Treatment abroad". This phrase, which usually evokes images of brilliant clinics abroad, should rather be alarming in this context. Foreign countries may mean, for example, China or South American countries, in which, as noted, the standards of clinical trials are low, and the data are not always transparent.

• "We have been conducting successful stem cell therapy for more than 20 years." It is worth not being lazy and checking with the legislation of the country that offers this treatment. In Russia, for example, the use of stem cells for treatment has been allowed only since the beginning of 2017. Therefore, the previous 20 years, the activities of such clinics were apparently very ambiguous.

• "Publications". On some sites you can find a list of publications on the topic confirming the effectiveness of therapy. However, it is often enough to click on the link to find that the therapy has shown some results on mice or on individual cell cultures. Which, of course, does not imply the effectiveness and safety of this method for people.

The III Congress on Regenerative Medicine will probably tell us about the latest achievements from the world of stem cells. But while they remain the subject of active debate and research, we recommend that you be attentive and follow their fate with interest from a respectful distance.

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