Stem cells: How to distinguish science from myth-making? (1)
O.Mynbayev, Gazeta.kz
Not so long ago, a Kazakh statesman, speaking on television, said that the Nobel Prize in Physiology and Medicine for 2007 was awarded to scientists for discoveries made in the field of stem cells.
And he added that for similar work, for example, we in the Republic of Kazakhstan do not need to conduct any deep fundamental research, because there is a scientific base, and everything is already known. And we have, as it were, scientific evidence to continue working in this direction.
Since the professor is a well-known scientist, and for many his words mean the truth firsthand, we asked for an alternative opinion in order to get acquainted with the European scientific point of view on this issue.
For comments on the topic, the site turned to Dr. O. Mynbaev, the author of several publications in our publication. Master of Medical and Pharmaceutical Sciences, member of many international scientific and scientific-practical societies, winner of prizes: Society of Laparoendoscopic Surgeons (on a multidisciplinary scientific project); European Society of Gynecologists-Endoscopists (named after Raoul Palmer); American Association of Gynecologists-Laparoscopists (named after Jeremy Hoffman); American Society of Reproductive Medicine and Medical Association, Founder and head of international research groups with headquarters in Leeuwen, Belgium.
In particular, we wanted to know for what merits scientists were given the Nobel Prize in physiology and medicine. Does their discovery concern the use of stem cells in the clinic? What are fetal stem cells in general? We also asked him to comment on the scientific discovery of our Kazakhstani scientists in this field.
And that's what they heard.
The information circulating in the media that scientists have received the Nobel Prize in Physiology and Medicine for discoveries in the field of stem cells is rekindling interest in mysterious cells, both among specialists and among ordinary people.
Now many will have a desire to try them on themselves in order to cure something, strengthen some organ or, finally, just rejuvenate.
Since there are already a lot of myths on the Internet, as well as scientists in real life dealing with this problem, there are also a certain number of charlatans who use the moment to earn money and fame.
The Nobel Prize in Physiology and Medicine – recognition of the merits of scientists who gave the world the key to solving the submolecular mechanisms of physiological processes and diseases – has NOTHING to do with the use of stem cells in clinical practice.
Although journalists dubbed the merit of the 2007 Nobel laureates as a "discovery in the field of stem cells," Professor Mario Capecci from the Howard Hugh Medical Institute, University of Utah (USA), Professor Oliver Smithies from the University of North Carolina (USA) and Professor Martin Evans from Cardiff University (UK) received the Nobel Prize for the development of targeting technology a specific gene in the genome. Subsequently, this technology led to the birth of a mouse with a "switched off" (knockout) or "added" gene, i.e. the target gene.
Briefly about the essence of the discovery. If a certain gene plays an important role in the development of a disease, then the experimental mouse shows, for example, signs of this disease. And with the help of embryonic stem cells, it is possible to deliver modified genetic material (recombinant DNA) into the cells of mouse embryos, so that in the future this information is inherited, and their descendants will manifest or disappear this or that disease – depending on the shutdown or inclusion of this target gene in the embryo genome.
The wording of the Nobel Committee states that the prize is awarded for a series of revolutionary scientific discoveries in the field of stem cells and DNA recombination in mammals.
The scientific discoveries of these scientists made it possible to create an extremely powerful technology called "targeting genes in mice." This technology is already being applied, in fact, in all areas of biomedicine – from basic sciences to the development of new therapeutic approaches.
In order for the reader to understand this omnipotent technology, I want to give a little explanation.
For geneticists, DNA recombination means merging paternal genetic material with maternal to form a new genetic code for germ cells. American scientists M.Capecci and O. Smitis have been working for a long time to solve the problems of specific modification of genes in mammals using homological recombination. As you know, Professor Joshua Ledeberg received the Nobel Prize for discoveries concerning genetic recombination and the organization of genetic material back in 1958. Using homologous recombination methods, M. Capecci showed the possibility of correcting a defective gene with the help of new DNA.
O. Smitis initially tried to "fix" mutated human genes. He suggested that some hereditary blood diseases could be cured by correcting mutated genes in bone marrow stem cells, which is the cause of this pathology.
But since the stem cells used by these scientists in the initial stages of the study did not make it possible to obtain animals (mice) with the target gene, they used embryonic stem cells as a means of transferring modified DNA to germ cells so that this information could be inherited further.
M. Evans first worked with cells of embryonic tumors – carcinomas – in order to use them as a means of transferring modified DNA into the germ cells of mice. However, when the carcinoma cells, due to the presence of defective chromosomes, could not participate in the formation of germ cells, he received suitable embryonic cells from mouse fertilized eggs.
Thus, by 1986, the efforts of scientists working in various laboratories and universities led to a revolutionary discovery – the possibility to study the function of a certain gene to knock it out of the game (knockout) or, conversely, insert an additional gene in the process of forming genetic material for offspring.
An article about the birth of the first mouse with a knockout gene was published in 1989, and this opened a new era in genetics.
Currently, gene knockout technology is used in numerous laboratories with a wide range of scientific and practical purposes, which cannot be described in a brief and even more popular, and not a scientific article.
More than 10,000 genes have already been studied in this way, and in the coming years, the functions of all genes in mammals will be studied. This technology can help us understand the role of each gene in the development of the embryo, the mechanisms of both physiological (aging) and pathological processes (causes of cancer, hereditary and other diseases).
Thus, with the help of genetic engineering, more than 500 mouse models of various diseases in humans (cancer, diabetes, cardiovascular, neurodegenerative and other severe ailments) have been obtained.
This technology in the future will give us the opportunity to ensure the birth of healthy children by turning off or, conversely, activating healthy genetic material from parents. I.e., it will be possible to take only normally functioning genes and exclude mutated ones, diagnose the disease before the onset of clinical symptoms and, accordingly, carry out preventive therapy or take preventive measures.
As is known, the cause of the development of diseases at the genetic level is associated with mutation or breakdown of genes with subsequent dysfunction of certain mechanisms associated with the work of this gene / group of genes.
Subsequently, there is a shortage, excess or dysfunction of biologically active substances that have certain properties necessary for the full functioning of our body. This causes the development of the disease. If the mutation occurs in somatic cells, then the individual himself is ill. If the mutation occurs in the cells of the sex glands (egg and sperm), then this pathology is inherited.
Based on this, if we start talking about the contribution of the above-mentioned Nobel Prize laureates to the field of stem cells in clinical practice, it will turn out like in that catch phrase: "I'm telling you about Thomas, and you're telling me about Erema!".
Are stem cells a panacea for all ills, or are we wishful thinking?
There are always contenders for the laurels of the discoverer for significant achievements of science, and now such a phenomenon is observed about stem cells.
Thus, in the Russian-language literature, it is believed that the Russian scientist A.A.Maksimov in 1908, having put forward the unitary theory of hematopoiesis, used the term "stem cell", and thus, 100 years ago, predetermined the now fashionable direction of science.
The first scientific works in this field in English-language literature date back to the 60s of the last century. The first publication of J.Altman and J.Dasa (1960), despite the fact that their data indicated the presence of stem cells in nerve tissues, remained out of sight of the medical community. And all thanks to the well-established opinion about the impossibility of renewing nerve cells and the authority of the great Spanish neuroanatomist and histologist Santiago Ramon y Cajal.
In the early 60s, E. McCulloch and J.Till found self-renewing cells in the mouse bone marrow. Further scientific research in this direction led in 1968 to a successful bone marrow transplant, which was performed by Dr. Robert Good from a healthy donor brother to a seriously ill 5-month-old boy (recipient brother) with severe combined immunodeficiency.
American scientist Edward Thomas, together with Joseph Murray, received the Nobel Prize in 1990 for the development of organ and bone marrow transplantation technology. The contribution of Edward Thomas himself was the development of methods and principles of bone marrow transplantation in the treatment of leukemia.
Indications for bone marrow stem cell transplantation are: leukemia, lymphoma, multiple myeloma, volumetric tumors and aplastic anemia, in order to replace stem cell deficiency resulting from the elimination of malignant cells after myeloablative chemo/radiotherapy.
Autologous cells are own cells from the umbilical cord blood, bone marrow or peripheral blood of the patient. Homologous are cells obtained from monozygotic twin brothers or sisters, and allogenic are cells obtained from healthy HLA–identical (immunologically compatible) donors.
Mesenchymal stem cells of the bone marrow give rise to cells of many organs and tissues, including blood cells
Stem cells have great therapeutic potential for the restoration of damaged tissues and organs, so they are of great interest to both scientists and practitioners.
In popular parlance, stem cells are called primitive cells that exist in all multicellular organisms and can turn into any type of tissues and organs.
These cells, for a number of reasons, only multiply, without signs of differentiated (specialized) cells of any specific tissues and organs.
They have only special genetic information designed for endless reproduction and long-term existence. In these cells, the ability to differentiate is suppressed by certain mechanisms. But when these cells lose the mechanism that restrains the process of differentiation, they begin to turn into cells of certain organs and tissues, i.e., "specialize", after which they lose the ability to divide indefinitely, and their lifespan becomes predetermined. After working out, differentiated cells die and make room for new cells with similar functional responsibilities. The lifespan of specialized cells varies: in some cells it is only weeks and months, in others it is years and decades.
Stem cells, according to their ability to give rise to various organs and tissues, are also divided into several types. The so–called totipotent cells can turn into fetal and placental tissues, and pluripotent cells can turn into tissues of three germ leaves, i.e., into all fetal tissues and organs.
Multipotent cells can only turn into cells of a certain family, i.e., one organ or one system, for example, hematopoietic stem cells. Unipotent stem cells are cells capable of multiplying and turning only into a specific cell or tissue type (hepatocytes, myocytes and other cells).
Stem cells are divided into several types and depending on the source of their origin. Cells derived from the internal mass of a blastocyst (an embryo at one of the early stages of development, consisting of several hundred cells) are called embryonic stem cells.
Cells found in tissues and organs are called adult stem cells. Cells derived from fetal cord blood are called umbilical cord stem cells.
Although the ideal stem cells are cells derived from bone marrow, this method is time-consuming and requires surgical intervention. Since in order to obtain sufficient material from the donor, it is necessary to perform multiple puncture and bone marrow suction. This procedure is performed under anesthesia.
For the use of stem cells obtained from the donor's bone marrow, full immunological compatibility between the donor and the recipient and suppression of the patient's immune system before bone marrow transplantation, plus further use of drugs that also suppress the immune system, is necessary. Therefore, in certain situations, it is considered effective to use autologous stem cells obtained from the bone marrow of the patient himself.
Thus, a randomized multicenter trial of the effectiveness of bone marrow cells for the treatment of myocardial infarction called Bone Marrow Transfer to Enhance ST Elevation Infarct Regeneration (BOOST) showed that transplantation of autologous bone marrow cells into ischemic areas can improve the function of the left ventricle of the heart after myocardial infarction.