The Year of Stem Cells
Stem progress: new opportunities in cancer treatment
Nikolay Kukushkin, RIA NovostiBone marrow stem cell transplantation after radio or chemotherapy is by far the most reliable method of combating many forms of blood cancer.
One of the main problems of this approach is the complexity of reproduction of such stem cells – in a healthy person, their number does not change much. Researchers from the University of Pennsylvania have discovered a mechanism by which stem cells in the bone marrow maintain their number unchanged. This study is just one of many breakthroughs this year in the field of regenerative medicine.
A look into the futureThe year 2013 in biology can be called the year of stem cells.
On the other hand, already in 2014, such a definition will almost certainly seem ridiculous. Modern medical science is more often developing not by leaps and bounds, as happens when very little is known about the subject, but by a continuous and avalanche-like process in its dynamics, in which the hard work of thousands of scientists around the world is steadily eroding the granite of science. This happens, for example, with cancer biology. It is difficult to single out key discoveries in this vast and diverse field of science. Despite this, the average survival rate of cancer patients has increased sixfold since the seventies.
Something similar happens with stem cells. The path to regenerative medicine – the treatment of diseases not by "patching holes", but by growing "spare parts" – is complicated and thorny. It may seem to the layman that scientists are unsuccessfully struggling to solve some critical problem on which everything depends. This could be true if we were trying to unravel a certain riddle of nature and find an answer hidden from us to a clearly posed question. In fact, there is no answer, or even a question, in fact: the scientific community is trying to invent something from scratch that nature has never heard of. And if anything, he's not so bad at it.
This year, the number of amazing scientific papers devoted to stem cells in one way or another is breaking all records. Some scientists print three-dimensional structures from them on 3D printers. Others grow teeth, kidneys, liver and even "mini-brains" on their basis. Still others are developing methods that make it possible to turn stem cells into nerve cells with one click.
This year, for the first time, it was possible to obtain human embryonic stem cells by transplanting a nucleus from an "adult" cell. Dolly the sheep was once raised from cells obtained in this way, and then a whole zoo of less advertised, but healthier animals. No one is going to produce cloned people, but the prospect of growing new organs from their own (and therefore ideally compatible with the body) skin cells can now be discussed not only in the context of a science fiction film.
Finally, in 2013, stem cells obtained from adult donors (and not from embryos) for the first time went outside the laboratories. Japan has started clinical trials of macular degeneration therapy using stem cells. Researchers in other countries lag quite a bit behind their Japanese colleagues. For example, in Scotland, scientists have already been granted permission to produce synthetic blood (also based on the use of stem cells), which will be tested in the clinic in the future.
Embryos and adultsGenerally speaking, a "stem cell" is a collective term combining several things that have little to do with each other.
Common to all stem cells is the ability to specialize into different types of cells. In some variants (as, for example, in the case of embryonic stem cells), this ability extends to everything in the body in general: from one fertilized egg, muscles, brain, and skin are eventually obtained. In other cases, stem cells can only give rise to certain types of tissues. For example, blood stem cells in the bone marrow give rise to both red blood cells (erythrocytes) and, for example, lymphocytes, but it will not be possible to grow the retina of the eye or the spleen from them.
Stem cells also differ in origin. The most obvious source of them is human embryos. Embryonic stem cells have been actively studied since the eighties. They are mainly taken from unused embryos obtained during in vitro fertilization. The use of embryonic stem cells has a number of advantages, but it is associated with understandable ethical difficulties. In addition, it excludes the possibility of obtaining cells and tissues that exactly match the genotype of the donor – after all, to form an embryo, you need to "shuffle" genes from two people.
Most of the high-profile studies today are devoted to induced stem cells, that is, artificially created on the basis of an "adult" cell that has already decided on its "profession". Such "professional" or differentiated adult cells (for example, skin cells) must first be made undifferentiated – that is, made to forget the "profession". The invention of this process, by the way, was awarded the Nobel Prize last year. The resulting induced stem cells can already be used to produce any tissues and organs – at least in theory.
Blood stem cellsAgainst the background of research on embryonic and induced stem cells, the work devoted to more specialized types of stem cells recedes into the background.
Nevertheless, at the current stage of the development of medicine, they are no less, and perhaps even more important. The most obvious example is blood stem cells located in the bone marrow. They are used in radiotherapy of various forms of blood cancer.
The strategy in such cases is generally the same. Cancer is a disease that begins when some cell - for example, a blood cell – loses control of its own division and begins to multiply uncontrollably. Exposure to gamma radiation or powerful chemotherapy can destroy the ability of cells to multiply and thereby stop the progression of cancer. But in addition to cancer cells, stem cells are also "sterilized", whose division is necessary for the constant renewal of normal blood cells. Therefore, patients after radiotherapy need a bone marrow stem cell transplant. There are two options. In the first case, stem cells are taken from the patient himself – before he is irradiated with radiation. This ensures perfect compatibility, but creates a risk of cancer recurrence if the original problem was related to the defective genes of the patient – after all, after the transplant, the genes will remain the same. The second option involves the transplantation of cells from a compatible donor – it is in the search for such a donor that its main difficulty lies.
Despite the fact that blood stem cells in the field of regenerative medicine are in the shadow of more "powerful" stem cells – embryonic and induced – this year and their research has made a step forward, and quite recently. One of the serious problems of therapy based on blood stem cells is the limited number of them: the precious bone marrow obtained from a donor is not infinite, and it is not so easy to multiply blood stem cells, unlike induced or embryonic ones. A new study by scientists from the University of Pennsylvania may solve this problem in the future.
Be fruitful and multiplyThe fact is that only a certain number of blood stem cells are maintained in the body.
When they divide, one cell remains a stem cell, and the second takes the path of differentiation. This division is called asymmetric. The medical task is to increase the number of stem cells needed for transplantation – but this can only be done in the case of symmetrical division, when two stem cells are obtained from one stem cell. Quite a bit is known about how exactly division asymmetry is achieved.
American researchers have found out that blood stem cells can be made to divide symmetrically if one of the proteins involved in the division process, myosin type II, is blocked. It participates in the formation of constriction between dividing cells. In humans, there are two variants of such a protein – myosin IIA and myosin IIB. It turns out that normally in the process of stem cell division, myosin IIA is equally distributed between daughter cells, but myosin IIB is concentrated only in one of them. What makes myosin IIB so special is not entirely clear, but, apparently, it "pulls" into one of the daughter cells some important factors that already determine whether the cell is a stem cell. If you "turn off" myosin IIB genetically, then the division becomes symmetrical: two identical stem cells are formed from one stem cell!
The only problem at the moment is that we cannot easily block myosin IIB without affecting myosin IIA, which is needed to maintain cell viability. In the laboratory, this can be achieved by genetic methods – which the authors of the study did – but in practice this approach is more difficult to use. Ideally, it is required to obtain a substance that could block only one of the two types of myosin II. So far, only a compound that simultaneously blocks both variants of the protein is known. But even if it is used for a short time, it gives promising results.
It turns out that cells can survive for some time without myosin IIA, and simultaneous blocking of myosin IIB still forces them to divide symmetrically. Therefore, if the blockage is removed in time (before the cells begin to die), the number of stem cells will increase. But in the future, a specific myosin IIB inhibitor can make the "reproduction" of stem cells a routine procedure – and its detection with modern biology capabilities is a matter of technique.
The discovery of researchers from Pennsylvania could potentially make life much easier for doctors and patients. The possibility of relatively easy reproduction of stem cells means that the amount of biomaterial taken from the donor can be significantly reduced. Theoretically, the possibility of cultivating these cells means that genetic manipulations can be carried out on them before transplantation – for example, turning off defective genes, which cause cancer. If such methods appear, then there will be no need to find a compatible donor: it is impossible to find a better donor than the patient himself, and any problems with his cells can be solved in vitro.
Today, few people have doubts that stem cells are the foundation of the medicine of the future. The only question is when real methods of treatment will be built on this foundation. Judging by the speed of development of this area, it is not long to wait.
Portal "Eternal youth" http://vechnayamolodost.ru18.12.2013