Topical issues of gene and cell technologies: results

At the end of May, the V International Symposium "Topical Issues of Gene and Cell Technologies" was held in Moscow, organized by the Institute of Human Stem Cells. According to the press service of ISKCH, this year the symposium gathered a record number of participants, thereby confirming the status of one of the leading Russian scientific and educational platforms for the exchange of experience in the field of biomedical technologies.

In his welcoming speech, Artur Isaev, Director General of the Institute of Human Stem Cells, noted that brilliant scientists and world-renowned researchers, whose achievements in the field of cellular and gene technologies are the most significant and interesting, make presentations at the symposium. "Today, people have gathered here, without exaggeration, creating the face of the future and we have the opportunity to touch it and see what it will be like."

Mitsuo Oshimura (Japan) in his report "Technology of artificial human chromosomes for gene and cell therapy" outlined the features of the technological stages of creating artificial chromosomes, focusing the audience's main attention on the advantages of this approach and the possibilities of its practical application. The artificial human chromosome (Human artificial chromosome, HAC) is a "microchromosome" created by methods of chromosomal engineering, containing the genes necessary for developers.

The main advantage of HAC is stable long–term expression without affecting the genome of the host cell. Professor M. Oshimura spoke about the possibilities of using HAC to create induced pluripotent stem cells with desired properties, and to treat a number of hereditary diseases with their help. According to Professor M. Oshimura, his research is at the in vitro stage. However, even now the innovation and importance of HAC technology is beyond doubt.

Patrice Bourgeois (France) in his report "NMD-chip: the European project for the diagnosis of neuromuscular diseases based on DNA-chipping technology" spoke about the joint activities of 13 scientific groups from 8 European countries aimed at creating a highly sensitive, effective and productive technology for the DNA diagnosis of neuromuscular diseases based on the use of special chips. Currently, the diagnosis of such diseases is not effective enough, characterized by a high percentage of false results. Research is carried out in two directions at once: identification of new mutations in the European population with the creation of a database and their introduction into the diagnostic chip.

Shukhrat Mitalipov (USA) in the report "New reproductive technology for the prevention of mitochondrial diseases" presented the results of studies of the mitochondrial genome. Despite the relatively small, slightly more than 30, number of mitochondrial genes and a significant number of their copies at the cellular level, with the accumulation of a certain percentage of mutations, the manifestation of diseases caused by these mutations occurs.

Basically, we are talking about quite numerous hereditary neuromuscular pathologies. Sh. Mitalipov explained the essence of the technology he is developing to eliminate such diseases, which consists in replacing the cytoplasm of an egg containing a high percentage of mutations of mitochondrial genes. The chromosome-containing region of the cytoplasm of the "sick" egg is transferred to a healthy egg, previously deprived of a nucleus. At the preclinical stage, this technology has been well researched and worked out by Professor Mitalipov's scientific group, including on monkeys. At the moment, work is underway to organize clinical trials.

Sergey Lvovich Kiselyov (Russia) presented to the participants the report "Cells with induced pluripotency as a model of neurodegenerative diseases", in the first part of which he spoke in detail about what induced pluripotent stem cells (iPS cells) are and how they can be obtained. The second part of the report was devoted to the extensive possibilities of using such cells.

S.L. Kiselyov paid the greatest attention to the use of iPS cells obtained from cells of patients with genetically determined diseases to create a kind of cellular models – test systems. According to the professor, having "several" skin cells of a sick patient, it is possible to obtain a culture of iPS cells, which, naturally, will have the same genetic disorder. The resulting cell line can be used to study the pathogenesis of the disease at the cellular level, to test and select highly effective drugs, including personalized ones, for the purpose of disease therapy.

Roman Vadimovich Deev (Russia) made a report "The first in Europe gene therapy drug Neovasculgen: from basic research to routine clinical practice", in which he outlined the essence and results of clinical studies of the drug through the prism of specific, most relevant and frequently asked questions by cardiovascular surgeons about the mechanism of the drug and its effectiveness.

Also, R.V. Deev noted that out of 1,500 clinical trials in the field of gene therapy, about 20 are being conducted as part of the treatment of patients with cardiovascular pathology, Neovasculgen has already shown its effectiveness, while some drugs have gone the distance. Currently, only three gene therapy drugs are registered in the world, one of which is Neovasculgen, the other two drugs are approved for use in China and are intended for the treatment of patients with malignant tumors of the neck and head.

Afanasyev Boris Vladimirovich (Russia) in his report "Experience in the treatment of hereditary diseases with hematopoietic stem cell transplantation, prospects for the use of gene therapy" spoke about the treatment of children with hereditary diseases of the hematopoietic system using the only currently possible method – transplantation of allogeneic hematopoietic stem cells.

Axel Zander (Germany) made a report "Genetically modified hematopoietic stem cells for the treatment of patients with HIV-associated malignant diseases", which became a logical continuation of the report of Boris Vladimirovich Afanasyev. Professor Zander outlined the relevance and complexity of the problem of treating patients with HIV-associated malignant diseases. Considering that there is no radical method of treating HIV infection, and the oncological pathology that has arisen requires hematopoietic cell transplantation, the problem of protecting transplanted cells from the human immunodeficiency virus becomes obvious.

Axel Zander spoke about the possibility of blocking the CD4 receptor of hematopoietic cells using gene technologies at the preparatory, pretransplantation stage, to level the CD4-mediated penetration of the HIV virus into cells. As a result, the cells to be transplanted become resistant to HIV and, in this regard, effective for the treatment of patients with HIV-associated malignant diseases.

Paolo Macchiarini (Sweden) presented an informative and informative report "The lessons we learned after performing allogeneic and biosynthetic trachea transplants and their significance for the creation of organs in the future". The first part of the report was devoted to the tissue engineering principles underlying surgical interventions performed by Professor Macchiarini. The concept of the technique is to combine the carrier and cells (multipotent mesenchymal stromal cells), incubation in a bioreactor and treatment with growth factors (erythropoietin) immediately before transplantation.

In the second part of the report, P. Macchiarini spoke about the use of tissue-engineered equivalents of the trachea (bronchi) obtained by using a carrier from a decellularized cadaver trachea. It turned out that, despite the success of the treatment of patients, at late follow-up, the transplanted material lost its "rigidity", and the cells migrated to the inner surface of the graft due to insufficient blood supply. The noted shortcomings served as the main development of a new synthetic nanostructured carrier. The tissue-engineered equivalent of the trachea obtained with its use is practically devoid of the disadvantages of "first generation" transplants.

While maintaining adequate biomechanical properties, the graft rapidly epithelized, the graft cells did not migrate into its lumen. All the provisions and theses of Paolo Macchiarini's report were illustrated with microphotographs, computed tomograms, 3D video circuits, which greatly facilitated the perception of the message. In conclusion, Professor Macchiarini spoke about the upcoming plans implemented on the basis of the Kuban State Medical University, consisting in the development of an effective technology for creating artificial organs not only of the respiratory, but also of the digestive system, as well as modification of the technology through the use of methods of induction of the recipient's cells to the transplant and increase its vascularization.

Mark Hedrick (USA), president of the American company Cytori Therapeutics, made a presentation "Adipose tissue stem cells and their clinical use" in which he spoke about the advantages of using hardware methods for isolating cell populations that allow obtaining "fresh cultures" suitable for immediate use. So, with the help of the Celution device developed by Cytori, right during the main surgical intervention, the patient's adipose tissue is obtained, minimal cellular processing is performed, and the resulting "fresh culture" is injected into the target area (breast plastic surgery, facial contouring, etc.).

The advantage of this approach over standard lipofilling is the prolongation of the effect – native adipose tissue, when used during standard treatment, quickly "resolves", while the "fresh culture", enriched with poorly differentiated cells of the "stromal vascular fraction", persists for a longer time. Mark Hedrick also spoke about plans to expand indications for the use of hardware methods of cell isolation, in particular, in the direction of cardiological pathology and the first results of clinical studies in this area.

Portal "Eternal youth" http://vechnayamolodost.ru05.06.2012