08 February 2008

Stem cells: How to distinguish science from myth-making? (2)

The beginning of the article: Stem cells: how to distinguish science from myth-making? (1)O.Mynbayev, Gazeta.kz

In the last century, the idea of widespread use of stem cells in practical terms had limitations associated with the lack of a safe and easily accessible source of material. Therefore, there was a search for him. Thus, the method of culturing mouse embryonic cells from the internal mass of the blastocyst was developed by M. Evans, M. Kaufman and J.Martin in the early 80s of the last century.

Further work on the study of mouse embryonic, human and mouse carcinomatous embryonic cells contributed to the development of technology for the production, reproduction and preservation of stem cells in many laboratories.

By the end of the XX century, there was a fierce battle between many leading laboratories in the struggle for primacy in obtaining embryonic stem cells from human material.

Therefore, Thompson's article with co-authors, published in 1998 in the journal "Science", was one of the triggers of the scientific boom in the field of stem cell research. In this work, they showed the possibility of obtaining human embryonic stem cells from fertilized eggs.

Today, numerous lines of human embryonic stem cells have been obtained in many laboratories around the world. There are scientific searches aimed at developing methods of using human embryonic stem cells in various diseases, but until today these cells have not been used in the clinic yet.

Currently, there are drugs that promote the release of stem cells from the bone marrow into the peripheral blood. Therefore, in clinical settings, the most commonly used stem cells are cells obtained from the bone marrow with the help of these drugs – colony-stimulating granulocyte growth factors.

In the future, in laboratory conditions, these cells are brought to condition, safety is determined in all parameters and used for many diseases.

The use of autologous stem cells derived from bone marrow is considered effective in certain situations (Fig. 1).

The figure shows a diagram of the stages of using stem cells from one's own bone marrow to a patient with mandibular cancer. The report on this work was published in the authoritative scientific journal "Lancet" in 2004. This patient had a part of the lower jaw removed due to cancer and a metal splint supported the soft tissues of the lower jaw and oral cavity. For 9 years, the patient lived with this tire and was fed through a probe. When a method of growing bone tissue from stem cells was developed, doctors suggested a treatment method.

схема этапов применения стволовых клеток из собственного костного мозга больному с раком нижней челюсти
A sufficient portion of stem cells (2) was extracted from the bone marrow (1), and these cells were planted on a specially designed structure (3) made of titanium frame and bone meal. Then the whole structure was transplanted to the patient (4) in the chest area. Within seven weeks, bone tissue resembling the shape of the previously removed part of the lower jaw was formed (5). Surgeons removed the metal splint (6) and implanted bone tissue (7). Subsequently, this patient could eat independently. X-ray image of the patient before (6) and after (7) implantation of the bone tissue of the lower jaw.

According to the same principle, various autologous (own) cells are currently used to replace damaged organs, for example, chondrocytes to replace cartilage tissue with impaired joint mobility (Fig.2).

Восстановление поврежденной поверхности суставов с помощью хондроцитов, полученных из собственного хряща
Fig.2. Author Meruert Mynbayeva. Restoration of the damaged surface of joints with the help of chondrocytes obtained from their own cartilage: a – normal joint, b – development of joint pathology (arthrosis), which causes pain and disrupts joint mobility; c – taking of cartilage tissue using arthroscopy; d – cultivation and reproduction of chondrocytes from cartilage tissue; d – removal of pathologically altered area tissues on the surface of the joint; e – formation of a "hole"; g – transplantation of chondrocytes; z – chondrocytes germinate and create a smooth surface in the joint and the patient recovers.

There is an intensive scientific search for possible ways of using embryonic stem cells, but at the moment there is still no data on the use of these cells in humans.

The main significant events regarding stem cells in the scientific world, with the exception of the above, can be considered the following publications and reports of scientists.

So in 1978, hematopoietic stem cells were found in the umbilical cord blood of newborns. Stem cells from nerve cells were cultured in 1992 under the name neurosphere.

In 1997, the origin of leukemia from hematopoietic stem cells was clarified, which indicated the presence of cells similar to stem cells in cancerous tumors. High plasticity (multipotency) stem cells were simultaneously shown in 2000 by several groups of scientists.

Scientists from Advanced Cell Technology, Inc. (ACT) in 2001 reported that they had cloned human embryos up to the 4- and 6-cell stages to obtain embryonic stem cells.

In 2003, Dr. Songtao Shi of the (NIH) National Institutes of Health (USA) discovered a new source of stem cells in baby teeth in children. British scientists from Kingston University in 2005 announced that they had discovered new forms of stem cells, like two-faced cells, similar to embryonic stem cells, but derived from umbilical cord blood.

In 2006, an artificial liver was developed using umbilical cord stem cells. In 2007, stem cells were obtained from amniotic fluid. It is believed that this method facilitates the ways of obtaining embryonic stem cells and the application of cell technology in practical medicine.

One of the intriguing news of recent years has been the production of induced pluripotent stem cells, which are designated as "iPS cells" or "iPSCs". The editor of the news of the journal "Nature Reports Stem Cells" Monya Baker last year made a report that two groups of scientists managed to transform human skin cells into cells that are practically indistinguishable from embryonic stem cells.

At the same time, they used only three genes to transform these cells! This was enough to turn the life of these somatic cells (skin) back! Back to their embryonic stage.

Further development of this technology may lead to the fact that all the tissues and organs necessary for the renewal of the body will be made from the cells of the patients themselves. This discovery gives, on the one hand, advantages in the treatment of patients by using their own stem cells, on the other – new opportunities in the study of molecular mechanisms of disease development.

The traditional opinion that embryonic cells can give cells for any tissues and organs, and the possibility of differentiation of adult stem cells is limited, and they can only give certain types of cells, is now in doubt. Thus, the previously discovered feature of adult stem cells – their plasticity or variability in certain situations, has been confirmed in the discoveries of recent years that it is possible to reprogram somatic cells, in particular, skin fibroblasts. Moreover, the latest discovery provides much more interesting ideas for researchers – if it is possible to reprogram a cell, then perhaps in the future it will be possible to update a separate organ or even an entire organism according to the same scenario!

Which will outweigh: money, fame or morality?

Biomedical science is becoming one of the most scandalous branches of knowledge. Huge investments from public and private organizations, as well as opportunities to "hit the jackpot" attract the attention of not only true scientists eager to explore the unknown, but also scammers and charlatans.

On the one hand, despite the lack of scientific evidence, in order to earn money, the use of cellular material of various origins called "stem cells" is carried out.

On the other hand, some scientists, manipulating the results, took wishful thinking for reality. For example, the scientific circle of Seoul National University is shaken by scandal after scandal related to stem cells and cloning.

The first scandal was called "Hwang Gate". In 2004, Hwang Woo-seok published an article in the journal Science, where he claimed that he had achieved a breakthrough in the use of a new technology for growing stem cells of his patients, about the breeding of 11 colonies based on stem cells from different donors and having a genotype identical to the donor.

Recently, the commission of the main South Korean university, Seoul National University, published the final results of the investigation into the scandal surrounding Professor Hwang Woo-seok. The Commission confirmed the fact that scientists falsified data on the world's first cloning of human embryonic stem cells, which made a splash in 2004. The pride and shame of the Korean nation in one person, now a former professor Hwang Woo Seok, who lost everything (reputation, titles, etc.), with tears in his eyes asked for forgiveness from his compatriots.

Now Hwang-gate has been continued with another Korean professor Lee Byung-chun, who announced... cloning of a wolf.

On March 27, 2006, a group of scientists from this university, led by their professor of the Department of Veterinary Medicine, Lee Byung Chun, made a statement about the world's first cloning of a wolf and published the results in the journal "Cloning and Stem Cells".

To check whether the she-wolves are really clones, the Seoul National University committee tested samples submitted by Lee Byung Chun's team in independent laboratories and proved that the results were falsified. Although the proceedings with Professor Lee Byung Chun are still ongoing, the Seoul press has already written that these scientists have caused enormous damage to the entire Korean nation...

Currently, publishers revoke published scientific papers when they find signs of falsification, plagiarism and other unfair mistakes that are unacceptable for scientific papers. The works of these scientists published in prestigious scientific journals have also been recalled. Now the works of such scientists are a visual aid for young scientists – what awaits them with a frivolous approach to scientific research!

P.S.

Upon arrival in Kazakhstan, I had a very close and long conversation with a professor who claimed that he was already growing stem cells. I hope there is no need to comment further on the erroneous incident now.

As for scientific discoveries in the field of stem cell research in Kazakhstan, unfortunately, our scientists are not published in reputable scientific journals, and therefore discoveries, even if they have occurred, remain unknown.

In our country, stem cells mean cells isolated from fetal tissue or abortive material. At the same time, for example, hepatocytes are isolated from the liver, chondrocytes from cartilage tissue, myocytes from muscle tissue, and so on. In the future, treatment is performed with the help of these cells.

However, the cells involved in the development of tissues and organs are no longer stem cells. They are, in fact, differentiated according to their location. Yes, stem cells are found and exist among them, but they are not numerous.

Therefore, when it comes to "fetal stem cells", it is first necessary to isolate stem cells from fetal tissues. The figure shows the classification of stem cells depending on the sources of their production in accordance with the stage of embryonic and postembryonic development: embryo, fetus, newborn and adult individual (Fig.3).

 классификация стволовых клеток в зависимости от источников их получения в соответствии со стадией эмбрионального и постэмбрионального развития

In the post-Soviet space, no one has yet isolated stem cells from fetal tissues. At least, I have not found any published works on this topic.

In principle, the term "fetal stem cells" itself is still hypothetical, since no one has presented these cells to the scientific world. That's why we are talking about the use of fetal tissues or cells, and not "fetal stem cells".

Based on this, this topic should be attributed to another category unrelated to science, and I am not familiar with scientific discoveries in this area made by Kazakhstani scientists, since significant discoveries are published in reputable peer-reviewed journals. And I would be only glad if such discoveries took place in Kazakhstan.

In order to use a foreign protein, especially a living cell, and for it to work, it is first necessary to completely turn off the recipient's immune system or complete immunological compatibility is necessary. Otherwise, the immunocompetent cells of the patient, i.e. the recipient, will immediately eat other people's cells, whatever they may be (stem or fetal).

In any case, the immune system reacts to the injected foreign biologically active material, and perhaps the patient will feel some effect.

Actually, there is a so-called "placebo effect" when patients are given a pacifier along with medications. This term was first used in 1955 by the American physician Henry Beecher.

Thus, in placebo-controlled trials, from 5 to 30% of patients feel an effect equal to recovery. And up to 5% of patients feel discomfort in the form of side effects of "treatment".

Chinese neurosurgeon Hongyun Huang became famous for the use of fetal cells for the treatment of patients with spinal injuries and Charcot's disease (amyotrophic lateral sclerosis). He injected fetal cells into the brain of patients by drilling holes in the skull.

As evidence of the effectiveness of his method, Dr. Huang showed several videos of patients before and after fetal cell transplantation. The price of such treatment is about 20,000 US dollars. When Dr. Huang was invited to Boston, he could not show anything intelligible to scientists from Harvard, therefore, scientists believed that there was a placebo effect.

So the miraculous effect of the introduction of fetal materials may be associated with a placebo. The authority of a specialist, inspiring confidence, multiplied with the help of the media to fame about the wonders of stem cells, do their job, but the effect is short-lived.

In Western European countries and in the USA, scientific research on the use of cells or materials from fetal tissues is not carried out. Since there is a fierce debate about the use of a fertilized egg to obtain embryonic stem cells from in vitro fertilization materials, there can be no question of using fetal material for any purpose. In the West, the use of cells derived from fetal tissues is considered unacceptable and immoral.

Therefore, I advise our scientists and doctors to be wary of representatives of pseudoscience and mythologists who have flooded our scientific space.

In conclusion, I would like to note that stem cells have a huge potential for the treatment of many diseases, but we are still looking for optimal opportunities for their proper use.

Any foreign materials create problems related to the immunological compatibility of the transplant with the patient's body, so special attention is paid to obtaining their own stem cells for each individual.

In my opinion, now the attention of scientists will be focused on a new direction of science – the reprogramming of somatic cells or induced pluripotent stem cells.

There is another important nuance: further research in this direction can shed light on some secrets of the eternally intriguing question of humanity – is the key to the lock called "rejuvenation" being selected?

Portal "Eternal youth" www.vechnayamolodost.ru08.02.2008

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