Stem cells: the present and the near future

There was a simple cell, it became a stem cellAnton Chugunov, "Biomolecule"

Stem cells (SC) have become a byword in the last decade, a source from which eternal youth and salvation from all ills are expected.

These expectations are most likely a little exaggerated, but by no means groundless: where else will you see such a miracle that a single living cell turns out to be a full-fledged organ ready for transplantation to a donor! There are thousands of times fewer stem cells in an adult organism than in embryos, and this is why there is a special interest in the latter as a source of "eternal youth". Fortunately, the ethical problem associated with the inevitable destruction of newly conceived life during the "extraction" of SC from embryos is gradually becoming a thing of the past: scientists are increasingly able to "reprogram" somatic cells into a state that is practically indistinguishable from the "stem" one.

Stem cell research has moved into the category of science that you can easily read about in a newspaper in the hands of a neighbor sitting next to you in the subway. Interest in this topic arose, of course, not from scratch: humanity has never been so close to the eternally coveted immortality as in the age of molecular biology. (At least, this is how it seems to journalists who promote modern achievements "among the people".) With the help of stem cells, we are promised at least a cure for most diseases, organ regeneration, transplantation without rejection, personal medicine, and, of course, youth and beauty. And these promises are by no means groundless: what is worth at least an experiment in which stem cells, using as scaffolding the frame of the heart of a dead rat, consisting only of connective tissue, completely complete the organ to a working state again [1]! Or, for example, another work is very good, in which embryonic stem cells have developed into a spherical two-millimeter formation of nervous tissue, very similar to the brain in the early stages of development [2]. But in addition to the absolutely fantastic industry of growing "spare" organs for yourself, you can also name more prosaic applications: for example, therapy with stem cells of cardiac tissue after a heart attack, which allows you to get rid of a scar in the myocardium that would otherwise remain for the rest of your life. In addition to the actual treatment of patients, stem cells will find (and are already finding) application in the field of testing new drugs for efficacy and toxicity, as well as for the study of rare genetic diseases on special "models" created with the help of SC. Many cosmetologists are also looking boldly into the future: already now you will often find statements about miracles produced by some kind of anti-aging agent, which is based on stem cells! (However, it seems that recently one of these funds was withdrawn, because on the basis of an independent examination it was found to be fraudulent.) Leaving these statements on the conscience of manufacturers of such cosmetics, we can nevertheless say with full confidence that stem cells have a great future in science, medicine, and the beauty industry.

The term "stem cell" (SC) was introduced into science not yesterday: at a meeting of the Society of Hematologists held on June 1, 1909 in Berlin, the Russian histologist Alexander Maksimov named blood cells that are capable of giving rise to several other types of cells. (Due to the fact that at that time the official language of science was German, and not English, as now, this word sounded like “Stammzelle”.) In the 60s, the formation of colonies of numerous differentiated cells from bone marrow cells was demonstrated, and in 1981, the American biologist Martin Evans for the first time isolated undifferentiated pluripotent stem cells from mouse embryoblast. In 1998, Thompson and Gerhart obtained the first immortal line of human embryonic stem cells (ESCs). In 1999, the journal Science recognized the discovery of stem cells as the third most important event in biology after the decoding of the DNA double helix and the Human Genome program.

The root of the hierarchy of stem cells (and all other cells of the body, too) is the zygote – the very first cell, which is the product of the fusion of an egg and a sperm. A zygote and several of its generations (during the first few days of embryonic development) are called a totipotent cell, that is, capable of giving rise to absolutely any tissue and organ, and indeed the whole organism. (By the way, identical twins are just the case when the zygote gives rise to not one, but two or several genetically identical organisms at once.) The branches of the hierarchy are pluripotent and multipotent (blast) stem cells, and the "leaves" are mature differentiated (unipotent) cells of body tissues. Mature cells are programmed for a limited number of division cycles, after which they die, being replaced by new generations; stem cells do not have such a restriction and can divide indefinitely, maintaining pools of stem and differentiated cells. However, with age, the population of stem cells decreases: if in embryonic development one ESC accounts for 10,000 differentiated cells, then in a person 60-80 years old – already one SC for 5-8 million.Genetically, all cells of the body (except sexual) are identical to each other, and all the difference in their structure and, consequently, functions (as well as the ability to divide and differentiate) is determined by the mode of operation (expression) of genes that differ in cells of different tissues.

(Strictly speaking, this is not quite true: erythrocytes do not have a nucleus at all, in some organisms the genomes of somatic cells undergo significant "contractions", mobile elements of the genome in different cells can move differently, but we will not dwell on this now.) Cell differentiation is controlled by cytokines - chemical signals (molecules), secreted by other cells.

So, the most significant characteristics of stem cells (for certainty, let's take ESCs) are:

• Totipotence is the ability to develop into a cell of any of the more than 350 tissues of the body;
• Homing is the ability to "feel" the gradients of chemokines and migrate to the zone of damage or active division, restoring the affected areas or taking part in the development;
• Gene expression redundancy – there are more than 3,000 mRNAs in the cytoplasm at the same time, which may be required only at later stages of embryo development;
• Telomerase activity. During DNA replication, the end sections of chromosomes (telomeres) are uncontrollably shortened, eventually affecting and damaging the structure of genes – which may be one of the natural mechanisms for limiting the number of division cycles and even the cause of aging in general. However, telomerase, an enzyme that lengthens telomeres and thereby removes the restrictions on division, acts in stem cells. (In this sense, stem cells are very similar to cancer cells, which are also able to divide indefinitely – only the latter do not contribute to longevity at all.)

What is wrong with embryonic stem cells?As already mentioned in the introduction, embryonic stem cells (ESCs) are an ideal example of totipotency, that is, unlimited ability to divide and differentiate.

However, if we think with an eye to practical applications – such as regenerative medicine or the cultivation of "spare" tissues and organs – then the main limitation in research becomes the well-known ethical problem associated with ESCs: to get them, you need to "pinch" a piece from the embryo, almost certainly interrupting the nascent life. This problem is so acute and has such strict legal restrictions that researchers often cannot work with human ESCs, even if nothing immoral needs to be done for this: if, for example, embryos that were not required during in vitro fertilization (IVF) are used as samples, having secured the consent of patients. The US law is particularly harsh on this score: George Bush personally banned, twice using the right of veto in Congress, state funding for any work in which human embryos could be destroyed.

However, the new US President Barack Obama, apparently, has already given legislative relief: in the summer of 2009, the first trials on the use of stem cells for the treatment of patients will begin. About ten paralyzed patients in one of the American clinics will receive a spinal injection of stem cells – precursors of oligodendrocytes (one of the types of cells of the central nervous system). This method has already been tested on laboratory animals, and in six months it will become clear whether it will help people [3].

Recently, there has been evidence that ESCs can be obtained from embryos without destroying them: if one of the blastomeres is separated from the embryo at the stage of four or eight cells, then an ESC line can be obtained from it, and in the meantime the embryo will continue to develop, at least until the blastocyst stage [4]. (No further observation was carried out based on the same ethical considerations.) And although, obviously, there is a method for obtaining ESCs that does not damage embryos – after all, the described procedure is practically no different from removing one blastomer for genetic screening during IVF – numerous ethical problems and public opinion resistance hardly promise this technique a great future.

Most likely, the breakthrough in advanced medicine associated with stem cells predicted in the next decade will be based not on ESCs, but on the so–called induced pluripotent stem cells (iPSCs, from Induced Pluripotent Stem Cell) - ordinary differentiated mature cells reprogrammed into a state of pluripotency.

Stem Cell SurprisesL. I. Korochkin, a major Russian biologist, one of the founders of developmental genetics and a prominent stem cell specialist, wrote in a popular article about stem cells in 2005: "... studying the behavior of stem cells has not shaken the ideas about the stability and irreversibility of cellular differentiation: a neuron will never turn out of a fibrocyte, plasma or parietal cell of the stomach and a skin cell will not arise from a neuron. <...> At the stage of terminal differentiation, the cell acquires a stable state and loses the ability to divide and various kinds of transformations" [5].

Only one year Leonid Ivanovich did not live to see an event that would undoubtedly have struck him to the depths of his soul: in 2007, the journal Science, which again published a rating of the most important discoveries (this time only for the past year), got two papers that reported on the production of induced pluripotent stem cells (IPSC) from mature, differentiated cells – using a kind of genetic reprogramming.

A pioneer in this field can be considered a Japanese biologist Shinya Yamanaka from Kyoto University, whose group was the first to report its results in the journal Cell [6] (Strictly speaking, this was not their first article, but it was noted in Science). The researchers managed to turn fibroblasts from human skin into cells very similar to ESCs in morphology, gene expression and ability to differentiate. This was done with the help of retroviral integration (or, as they say, transfection) into the fibroblast genome of four transcription factors (TF) – Oct3/4, Sox2, Klf4 and c-Myc (see box), which change the activity of genes and thereby the entire appearance and behavior of the cell. In the case of successful transfection, fibroblasts begin to change shape after a few days and form colonies of cells morphologically identical to ESC colonies, cease to synthesize proteins characteristic of fibroblasts and (such as the component of intermediate filaments vimentin), and begin to synthesize growth and differentiation factors characteristic exclusively of stem cells (Sox2, NANOG, REX1, FGF4 and others). Analysis of demethylation of promoters of "embryonic" genes, as well as the "histone code" – known mechanisms of regulation of gene expression (see box) – also confirmed that the genetic activity of induced SC is rearranged according to the "embryonic" type. In general, the gene expression profile determined using microarray technology turned out to be very similar (although not identical) to ESCs. Separately, it should be mentioned about the "inclusion" of the telomerase gene, an enzyme that ensures the "immortality" of SC.

To "help" the cells to rebuild in a new way, they are cultured in a medium of a special composition, replacing it after some time with a mixture optimized specifically for stem cells. In total, the described sequence of actions took 25 days, and out of ~5×10 ⁴ fibroblasts, 10 IPSC colonies were obtained – the "yield" turns out to be so low not only because of the low efficiency of transfection, but also because of less well-realized factors associated with gene expression.

In order to make sure that the obtained cells really have a broad ability to differentiate, their transformation into cells of all three germ leaves was demonstrated – in particular, into nerve cells or cardiomyocytes that demonstrate beating in culture (the ability to collectively perceive an electrical stimulus and respond to it). In addition, the totipotent properties of iPSCs were illustrated by the example of the formation of tumors – teratomas – in mice injected with these cells with genetically weakened immunity (this is a standard "stem cell test").

The mechanism of action of this "magic combination" of reprogramming proteins is not yet fully understood, however, it is known that two of the factors used – Oct3/4 and Sox2 – underlie the pluripotency of stem cells, actively working in them (but not in somatic cells). They activate the "stem and embryonic" genes in the cell, forcing the genes responsible for specialization, on the contrary, to reduce their activity. It is also known that these proteins cannot start the transformation of a mature cell on their own – apparently due to the methylation of the promoters of the corresponding genes and modifications of histones on which the DNA of chromosomes is "wound". According to one hypothesis, two other factors – c-Myc and Klf4 – modify the structure of chromatin, giving access to gene promoters. This is all the more likely because Klf4 can regulate the activity of histone acetyltransferase (an enzyme that "hangs" an acetyl label on the histone "bobbin") and thereby influence gene expression.

Interestingly, in stem cells that have finally "de-differentiated", the activity of genes delivered using retroviral vectors and caused this transformation is greatly reduced, and it seems that it is no longer required to maintain IPSC in the "stem" state. This circumstance allows us to hope that it will be possible to find a way to reprogram mature cells into a state of totipotence without integrating transcription factors into DNA under the control of viral promoters, two of which, used by Yamanaka, are proto-oncogenes: c-Myc and Klf4. And although after "reprogramming" these genes seem to "fall silent", about 20% of mice derived from stem cells whose genome contains externally introduced c-Myc and Klf4 suffer from tumor diseases, which, at least in part, is caused by the re-activation of these genes. ("Growing" mice from stem cells by planting them in an embryo and then crossing "mosaic" mice to obtain pure transgenic lines is a method awarded the 2007 Nobel Prize [7] as having received extremely widespread use in molecular biology.)

It should be noted that both c-Myc and Klf-4 are genes normally present in the DNA of a cell, but mostly inactive in the postnatal period. Delivery and integration of additional copies of them using a retroviral vector is required to cause superexpression, since viral promoters are just "sharpened" for this, although for the same reasons they are poorly controlled (which, ultimately, is the cause of oncogenicity).

An additional source of mutations can be the integration of genetic material into the DNA of human cells (by recombination with chromosomes), and, most likely, until a way is found to reprogram cells without transfection – only through one-time treatment with a set of any factors – the use of such SC in medicine will be very limited.

Let's do without oncogenesScientists are well aware that the success of the technologies they are developing for reprogramming somatic cells into stem cells depends on how safe their use will be.

First of all, the concerns here concern, of course, the oncogenic action of the c-Myc and Klf4 genes, and the need to embed something into the genome of the cell, on which human life will depend in the future.

Just a few months later, Yamanaka and his group report that they were able to obtain stem cells without one of the oncogenes they had used before, c–Myc [9]. It turned out that if you give the cells more time, then reprogramming takes place without this TF, albeit with significantly lower efficiency. (In the first mentioned work, scientists screened the culture for newly formed IPSC colonies 7 days after transfection, in the second – 14.) As expected, mice grown from these stem cells were no longer so susceptible to tumor formation: no such cases were registered during the observation. However, despite the fact that transfection in this case was performed by a set of three factors (not four), one of them is still a proto-oncogene - Klf4 – and the efficiency of obtaining IPSC has significantly decreased (by about 20 times, which in absolute numbers is <0.001%).

In another study, together with Yamanaki's work, noted in Science as one of the "breakthroughs" of 2007, scientists independently achieved similar results – induced the transformation of human fibroblasts into stem cells, practically indistinguishable from ESCs in basic parameters [10]. In this work, other inducing factors were used, a combination of which was selected from a set of genes active only in embryogenesis and in stem cell cultures. C-Myc and Klf-4 were excluded from the list of "applicants" in advance in order to try to do without proto–oncogenes, four genes sufficient for "transformation" were selected from the 14 remaining variants: two of them were the same as in Yamanaki's work – Sox2 and Oct4 - and the remaining two were different: NANOG and LIN28 (see inset). Scientists have shown that the activity of the Oct4 and Sox2 genes is absolutely necessary for reprogramming, while it was possible to do without NANOG or LIN28 (with a significant loss of efficiency and slowing down the process). Of course, in all cases, morphological, genomic and histological confirmation was carried out that stem cells were obtained, and not something else, and that they were obtained from somatic precursors, and not from other stem cells that happened to be in the cup.

The nutrient medium in which cells are cultured can have no less influence on the course of reprogramming than pluripotency inducer proteins. Thus, it has recently been discovered that the low-molecular-weight compound valproic acid, often used as a drug against epilepsy, can be used instead of oncogenic factor Klf-4 in the preparation of IPSC [11]. When added to the medium in which human fibroblasts were grown, valproic acid and three TF – Sox2, Oct4 and Klf-4 – reprogramming proceeds with a thousandfold increase in efficiency (i.e. 1% of cells are already converted into stem cells). When Klf-4 is excluded from the "reprogramming protocol", the efficiency returns again to the range of 0.001–0.01%, but this is without the integration of a gene potentially capable of causing malignant degeneration into the DNA chromosome. Valproic acid, a small organic molecule that, after having a certain effect, will be removed from the cell, turns out to be able to replace a retroviral vector that integrates into the genome and produces a potentially dangerous regulatory protein. The effect of valproic acid is explained by the fact that it is an inhibitor of histone acetyltransferase and DNA methyltransferase - enzymes that edit the structure of chromatin and are responsible for the activity of genes (see box). Klf-4 also has an effect on these proteins, which, apparently, causes their interchangeability. This fact reinforces the hope that eventually it will be possible to obtain stem cells without the use of retroviral transfection.

Stem cells from hairIn most of the mentioned studies, iPSCs were obtained by reprogramming fibroblasts (in the case of studies on human cells), and for mice there were successful examples for neurons.

But recently Juan Carlos Belmonte from the Salk Institute for Biological Research in California and a joint group of Italian and Spanish biologists managed to show that keratinocytes – cells of the stratum corneum and hair – are much better suited for reprogramming than "habitual" fibroblasts. In his work (however, a "full" set of inductors was used – Oct4, Sox2, Klf-4 and c-Myc) they demonstrated a hundredfold increase in the efficiency of reprogramming while reducing the duration of the experiment by half [12]. (Already on the 6-7 day after transfection, the first colonies of iPSCs appeared, almost indistinguishable from embryonic SC.)

"Provided that an effective and practically acceptable method of obtaining stem cells specific to each patient is available – and these conditions are clearly not met in the case of embryonic stem cells – cell therapy and transplantation will not cause rejection by the immune system, which will significantly bring us closer to the real use of stem cells in the clinic," says Belmonte, who Concurrently, he is the director of the Center for Regenerative Medicine in Barcelona [13].

Scientists explain such high efficiency of reprogramming not so much by the system and protocol of retroviral transfection chosen by them, as by the choice of keratinocytes as an object for "transformations". Their statistical analysis of the profiles of genetic activity of fibroblasts, keratinocytes and ESCs allowed us to conclude that keratinocytes are in some sense "closer" to stem cells, as a result of which less effort is required for them to adjust to a pluripotent phenotype. (In particular, the basal ("own") expression level of the c-Myc and Klf-4 genes is significantly higher in them than in fibroblasts, putting them "closer" to ESCs and explaining the greater ease of rearrangement.)

Figure 1. Preparation and characterization of induced pluripotent cells from keratinocytes (KiPSC). (a) Human scalp hair placed on a gelatinous matrigel nutrient medium moistened with a medium intended for stem cell cultivation. (b) The growth of keratinocytes in the nutrient medium from the hair trunk (but not from the bulb) becomes clearly noticeable after 5 days. Three days after that, the keratinocytes were "transplanted" into a separate cup, and three days later they were transfected with a retroviral construct containing the Oct4, Sox2, Klf–4 and c-Myc genes. (c) After some time, colonies of cells with a typical morphology for SC appear; these colonies are removed from the medium and transferred to a "substrate" of fibroblasts. (d) One of the KiPSK colonies 10 days after "transplanting". (e) At this stage, stem cell colonies with increased alkaline phosphatase activity (blue color) are already practically indistinguishable from both ESC and any other iPSCs. (e-k) immunofluorescence analysis shows that KIPSCS express all the markers typical for stem cells, including SSEA3, SSEA4, OCT4, SOX2, TRA-1-60, TRA-1-81.

In their work, biologists demonstrated the effectiveness of their proposed technique in the most elegant way possible: instead of using cell cultures, Petri dishes and other purely laboratory props, they simply took a hair from the head of one of the study participants, and demonstrated the formation of iPSCs in the area of the hair shaft (and not the bulb; see Fig. 1). This experiment confirms that the researchers observed precisely the reprogramming of keratinocytes, and not the proliferation of SC colonies present in the hair root (although their indirect influence is not excluded). The resulting cells, as expected, differentiated into representatives of mature specialized cells of all three germ leaves, including dopaminegric neurons (see Fig. 2) and cardiomyocytes performing collective beats in culture (see the video in the additional information to the article [12]). During "de-differentiation", the cells completely "forgot" their former appearance and stopped synthesizing the marker protein of keratinocytes – keratin-14 – and "turned on" genes characteristic of stem cells and embryonic tissues.

"Why exactly keratinocytes turned out to be more susceptible to reprogramming than all the other cells from the mass we tried is a big question," says Belmonte [13]. "However, knowing this reason is extremely important for the further development of both science and technology."Figure 2. KiPS cells differentiate in the tissues of all three germ leaves both in vitro and in vivo.

(a) Differentiation in the PA6 stromal cell environment with the addition of fibroblast growth factor FGF-8 and the homologue of the Sonic Hedgehog protein (SHH) leads to the formation of dopaminergic neurons with typical morphology and expression of the TuJ1 nerve tissue marker (green) and the tyrosine hydroxylase marker of dopaminergic neurons (red). (b-e) Examples of differentiation by this type. (e-i) Spontaneous differentiation into all three germ leaves at once can be observed on sections of teratomas (tumors formed in mice with genetically weakened immunity during injection of stem cells) when stained according to hemotoxylin/eosin (e) accepted in histology or by immunohistochemical method. Fluorescent labeling on TuJ1 (g), alpha-fetoprotein (h) and alpha-actinin (i) allows identification of ectoderm, endoderm and mesoderm, respectively.

Stem cells without transfectionResearch in the field of obtaining induced pluripotent stem cells from "ordinary" somatic cells is progressing by leaps and bounds, and there is no doubt that this task will soon be solved definitively.

(True, there will remain a much more fundamental problem: how to use the received iPSCs!) For example, more recently, a group of scientists from the Scripps Research Institute (California, USA) and the Max Planck Institute for Molecular Biomedicine (Munster, Germany) reported that they managed to obtain SC using only two TF, replacing the rest with low-molecular substances. However, the most interesting thing is that the list of "substituted" genes includes Sox2, which was considered absolutely necessary for reprogramming [14]!

"Our work proves that in the end we will be able to reprogram somatic cells into stem cells only with the help of chemical treatment, and without genetic manipulation at all," says Sheng Ding, professor of the Department of Chemistry at the Scripps Institute and head of the study [15]. "Given the contributions of a number of other working groups, it is safe to say that cellular reprogramming technology will soon become an integral part of practically important applications."The team led by Ding discovered two low-molecular heterocyclic compounds that allow reprogramming without integrating the Sox2 gene.

The "active substance" of this pair – known by the code name BIX – is (like valproic acid, which has already been discussed) an inhibitor of histone acetyltransferase and DNA methyltransferase - enzymes that regulate chromatin structure and gene activity. However, BIX itself provides very low reprogramming efficiency, and scientists were lucky enough to identify the second compound – known under the code BayK8644 – which, without affecting the activity of genes in any way (!) and being an agonist of the calcium channels of the cell membrane, allows to significantly increase the output of the process. Why this happens is not yet known for sure.

"We have not yet been able to establish the exact mechanism by which BayK accelerates reprogramming," Ding admitted [15]. - "We did not expect to discover that a small molecule affecting signal transmission and seemingly unrelated to pluripotency could "catalyze" it in this way. This may further allow the cell to be reprogrammed without violating its genetic integrity directly in vivo."And finally, we should tell you about the very recent work of the Yamanaki group, which, it seems, managed to carry out cellular reprogramming without integrating retroviruses into the genome [16].

Instead of a retrovirus, the researchers used an adenovirus, on the basis of which they built two plasmids – one with the Oct3/4, Sox2 and Klf-4 genes, and the other with the c-Myc gene – and developed a protocol for re-processing cells with these plasmids (on the 1st, 3rd, 5th and 7th days after the start of reprogramming), which made it possible to obtain the first IPSC colonies in 10 days, in whose genome there are no traces of integration of viral material. (At least, they could not be detected, no matter how carefully the analysis was carried out.) Repeated processing is required because the genes in this delivery method are not integrated into chromosomes, and, consequently, their product appears in the cell only for a short time. And, of course, the most advantageous thing in this way is that the genome of already "ready" stem cells remains unchanged. By the way, at the beginning of 2009, several papers have already appeared, which report on the successful reprogramming of somatic cells using only one viral vector carrying all the genes necessary for transformation.

So far, the effectiveness of such reprogramming, again, is significantly lower than when using retroviruses, and the principle itself has been demonstrated not on adult cells, but on mouse embryonic fibroblasts. However, the first drawback may be due only to a lower level of gene expression from the plasmid than from the DNA fragment embedded in the chromosome, and in this case it will certainly be possible to find a way out by optimizing the cell processing protocol. And there is no doubt that it will be possible to do the same on human cells.

ConclusionNo one doubts the prospects of research in the field of stem cells – it is not for nothing that the famous South Korean scientist Woo Suk Hwang, hoping to consolidate his priority in this area, could not resist the temptation and published in 2005 in Science deliberately falsified results regarding the production of ESCs by "transplanting" the nucleus of a somatic cell into an unfertilized egg, not from a lifeless embryo.

Fraud in such an actively developing field was, of course, discovered very soon [17], and the reputation of the researcher is now hopelessly damaged, but the field as a whole has made significant progress since then, and, as can be seen from this review, scientists are already practically on the threshold of stem cell technology that would suit everyone. (Except, of course, only the most ardent opponents of any molecular genetic work, which, according to some sources, is a mortal sin [18].)

And – for the umpteenth time – the work related to stem cells is called the breakthrough of the year. According to the journal Science, as well as many other publications, the "reprogramming" of somatic cells into stem cells (and into somatic cells of another type, bypassing the "stem" stage), the discovery of the specificity of keratinocytes in this regard and the first works that make it possible to do without genome modification are among the most important achievements of 2008 [19].

However, the most interesting thing is still ahead, of course: it is not enough to get IPSC and demonstrate on a model system that stem cells can form organs – we still need to learn how to transplant these organs to patients in need. According to laboratory studies, immunological rejection should not occur, but reality always makes its own adjustments, and the task may be much more difficult than one can imagine. Similarly, as long as stem cells can be used in "rejuvenating" cosmetic products, you will probably have to overcome a lot of difficulties and convincingly prove that playing with such a powerful tool as a stem cell will not harm human health (for example, under no circumstances will it trigger the process of tumor formation).

The first niche that stem cells will occupy in practically important activities in the very near future is the study of rare genetic diseases on SC cultures with a genotype that causes the disease. Many diseases cannot be properly studied because they are extremely rare, and patients with this disease are not easy to attract to the study for a number of reasons. Creating "models" of these diseases based on stem cells will help overcome this limitation and study diseases in more detail.

Stem cells will also find application in the field of testing drugs and other biological preparations, allowing you to quickly and effectively investigate the effect of various substances on cells of various types, thereby predicting the spectrum of activity of the future drug in different tissues and organs.

Neurodegenerative diseases, such as Parkinson's and Alzheimer's, are also "waiting" for the advent of stem cells – there is encouraging evidence that they will significantly contain the disease and even reverse the destructive changes caused by it.

The article was originally published in the journal Cosmetics and Medicine [20].

Literature1. Ott H.C., Matthiesen T.S., Goh S.K., Black L.D., Kren S.M., Netoff T.I., Taylor D.A. (2008).

Portal "Eternal youth" www.vechnayamolodost.ru25.02.2009