Throughout our lives, we gradually lose cells important for maintaining health, according to the online edition for girls and women from 14 to 35 years old Pannochka. net The loss of their populations responsible for certain vital functions causes many life-threatening age-related pathologies, such as Parkinson's disease.

Fortunately, therapies based on stem cell research give us the opportunity to restore such losses, literally renewing the junk tissues and organs..

However, to achieve this goal, it is necessary to solve a number of both scientific and moral and ethical problems..

Specialists had the opportunity to exchange experiences with researchers in whose laboratories degenerative age-related processes, if not reversed, then at least sharply slowed down in mice and other model organisms. These results rarely impress biogerontologists, who have been dealing with something similar for seventy years since the first caloric restriction experiments, but come as a pleasant surprise to oncologists and tissue engineers..

Cells of all trades: beware of fakes.

Due to the tragic intertwining of purely scientific issues with ethical, legal and religious debates about the status of embryos and the permissibility of abortion, ESC is an element of SENS that you are probably familiar with.. You have certainly heard that with adequate biochemical stimulation, ESCs turn into any type of cell - nerve (neurons), muscle (myocytes), cardiac (cardiocytes), kidney, etc..

The result of this process, " ESCs will be needed to successfully treat parkinsonism, spinal injuries, type 1 (juvenile) diabetes, amyotrophic lateral sclerosis (Charcot's or Lou Gehrig's disease), myocardial infarction, certain types of cancer, and other degenerative conditions, including aging itself..

Indeed, within the framework of a purely pragmatic, engineering definition of this process, which greatly clarifies the tasks that must be solved for the final victory over age, any death of the cells we need is a certain form of age-related damage.. And, therefore, is one of the main targets of SENS.

However, since the media coverage of this topic focuses on moral and ethical issues, and not on the really great medical potential of ESCs, you may not fully understand the key difference between ESCs and adult stem cells.. There are also fundamental differences between ESCs obtained from embryos stored in reproduction centers and those made from mature cells of a particular patient by fusion with oocytes, i.e.,. by a method (we will discuss it below) known as somatic cell nuclear transfer (SNTS). Therefore, to begin with, it is worth specifically dwelling on these issues..

ESCs are present only at the earliest stage of embryonic development, when the embryo is a blastocyst - a lump of cells that forms just a few days after the fusion of the spermatozoon with the egg. This stage is very short - by the time of implantation in the uterus, the embryo is much more developed. Blastocyst ESCs give rise to all the cells of a mature organism, but they themselves are not yet differentiated: they do not contain neurons, cardiomyocytes, insulin-producing beta-cells of the pancreas, etc.. Therefore, for the transformation of an embryo into a complex organism, ESCs require the ability to develop in any direction.. It's called pluripotency (totipotency).

In adult stem cells, the choice of maturation pathways is much narrower, and the reason for this is obvious.. They are formed at the later stages of development and are stored in certain tissues throughout our life as a reserve to compensate for their cellular losses.. As a result, the potential of specialization is limited to the acquisition of structural and functional features that are necessary only for a given tissue..

For example, stem cells of the hematopoietic system can turn into oxygen-carrying red blood cells, a variety of white blood cells (including lymphocytes) that protect us from infections, platelets necessary for blood clotting, but (contrary to some bold claims, which are discussed below) are not able to differentiate into either neurons or into. They, figuratively speaking, answer such a request directly and rudely: " That's right: they have a very specific job, they do it well (as a rule) and are not going to plug all the holes that appear in the body. Such a more or less limited range of potential specialization ("

Unfortunately, in many structures of our body, adult stem cells for current repair are not available at all - and, as you might guess, we are talking about the places where age-related cellular loss hits the hardest.. This situation, for example, is typical for a large part of the brain. For a long time it was believed that all of it gradually loses cells during normal aging, and in principle it is impossible to compensate for such losses..

A few years ago, this dogma collapsed - thanks in large part to the work of Frank Gage and his colleagues at the Salk Institute, who showed that the brain does contain stem cells that can renew certain parts of it.. As a result, the views of non-specialists swung to the other extreme: many decided that the presence of such cells allows the entire brain to maintain its youthfulness and original performance indefinitely..

However, this impression is also erroneous.. Stem cells capable of differentiating into neurons are produced in only a few areas of the brain.. We are talking about the region of the hippocampus, called the subgranular zone of the dentate gyrus, and about a fragment of the pancreatic zone, which supplies new neurons to the olfactory bulb (the brain structure necessary for the perception of smells).

Some of these stem cells are trying to repair parts of the brain affected by age-related diseases, according to some evidence, but the results of such attempts appear to be disappointing.. For example, after a stroke, a small number of subgranular zone stem cells change their usual characteristics and migrate to the affected site, but more than 80% of them die within the next weeks, and the survivors replace only 0.2% of the neurons that die in this incident..

Why do we retain the ability to update some areas of the brain, and not others, in particular that part of the cerebral cortex where long-term memory is stored, or their frontal lobes, which are responsible for planning and executing purposeful actions? Most likely, the fact is that the olfactory bulb and dentate gyrus are the only places where evolution has faced the need for regular replacement of neurons during the " Both of these areas are responsible for short-term functions that require constant renewal of their cell populations..

At the same time, adult stem cells, which are responsible for compensating purely age-related losses and preventing related pathologies such as Alzheimer's disease and parkinsonism, are not provided by nature.. This is explained by the following: although the prerequisites for such disorders lie in the ongoing molecular changes in the brain, the impairment of functions they cause does not have time to reach the threshold that affects the Darwinian fitness of our species within a relatively short period corresponding to the lifespan of a Paleolithic person..

Another example of a structure in which there is no natural replacement of dying cells is the thymus, one of the key organs of the immune system, necessary for the " The method of its restoration using stem cells is still only at an early stage of development, so there is no point in discussing it in detail.. I will only note that the proof of the validity of the concept used is associated with a rare, but very severe congenital pathology.

Thymus reconstruction.

The promise of using stem cells to prevent thymus involution stems from recent advances in the treatment of children with DiGeorge syndrome, a genetic anomaly whose victims are born with various defects, including underdevelopment and sometimes complete absence of the thymus - the latter case is called " Until recently, a full Di George usually meant a quick death.. Without producing mature T-lymphocytes, babies die within a few months after birth from infections that are safe for other people..

The obvious treatment is thymus transplantation, but this operation is very complicated.. The transplant needs a lot of oxygen, t. abundant blood supply, but to provide it without natural vascularization (t. development of a dense network of small blood vessels in the tissue) is difficult.

In addition, problems with transplanted organ rejection and homologous disease have long arose: sometimes some cells of the infant's bone marrow spontaneously turn into abnormal T-lymphocytes that do not recognize antigens of either the foreign thymus or the patient's own.. As a result, they violently attack all of his tissues - usually with a fatal outcome.. Moreover, donor T-lymphocytes often take up arms against recipient cells alien to them, rushing into a counterattack no less destructive for the body..

Recently, surgeons and immunologists from Duke University (USA) have developed a method of transplanting very thin sections of thymus tissue (providing maximum oxygen supply) implanted in the thigh of an infant, which guarantees a copious blood bath, along with a new immunosuppressive drug that specifically targets T-lymphocytes.. This approach is still considered experimental, but its results are constantly improving due to the use of additional innovations, and today, apparently, we can talk about relative success.. In a 2004 report from Duke University, five out of six patients did not die 15 to 30 months after the operation.. it significantly improved their survival.

If, instead of foreign transplants, we used stem cells from the infant himself, stimulating them to differentiate into thymus cells, and then transplanting them into the host, there would be no need for potentially dangerous immunosuppression. Then, if it was possible to force these cells to fill the scaffold that reproduces the complex structure of the thymus, including an adequate system of its blood supply, it would be possible to abandon the far from satisfactory replacement of this gland with a thin tissue section in favor of a "

Whether such a goal is achievable in the case of DiGeorge syndrome specifically is unclear, since patients with it simply have too little time.. However, if a foreign transplant is capable of producing viable T-lymphocytes, increasing the survival of infants born without a thymus, I consider it quite possible to introduce the patient's own cells, transformed into T-lymphocytes and, if necessary, built into a more complex tissue structure, into an existing one, but.

Similarly, in our heart there are cells known as " In the lab, they can be made to exhibit some of the molecular characteristics of stem cells.. However, their differentiation into cardiomyocytes has never been observed in the body.. By the way, closely related mesenchymal stem cells from other parts of the body have the same characteristics, but they are not capable of becoming cardiomyocytes in principle..

Be that as it may, it is known for sure: no cells of our body seek to heal the massive damage to the heart muscle caused by its oxygen starvation during myocardial infarction - this will be sadly confirmed to you by any patient who has survived it, and a cardiologist. And again, the reason for this is a cold statistical analysis of the results of a genetic lottery that stretched over many generations in a prehistoric habitat, scrupulously carried out by natural selection.. Myocardial infarction does not kill those under thirty, therefore, there is no reason for nature to provide our heart with a repair mechanism that its owner is unlikely to need until he dies of some other reason..

At the dawn of the public debate about ESCs, some respected laboratories published reports on the ESC-like plasticity of adult stem cells, in particular the ability of such cells of the hematopoietic system to spontaneously transform into liver hepatocytes and brain neurons.. Probably the most promising were the reports of their differentiation into cardiomyocytes after injection into the heart of rats with induced myocardial infarction, which led to the functional recovery of this organ.. Such publications caused the most serious resonance: some scientists even began clinical trials on humans: bone marrow cells from heart attacks were introduced into their affected heart muscles..

However, in independent laboratories, the pluripotency of these cells was not confirmed.. At best, their fusion with mature cells of the corresponding tissues was observed..

This may be of some benefit, facilitating the fate of their surviving cells after injury, for example, by secreting growth factors necessary for scarring or accelerating revascularization of the affected area, i.e.. development of new blood vessels. However, although such effects can provide a slight prolongation of the performance of our collapsing motor, hematopoietic stem cells are unable to reconstruct its tissue either in heart attacks or simply in the elderly, whose myocardium would not be damaged by rejuvenation..

medbe. en.