The RUDN scientist Dmitry Atyakshin presented innovative molecular histology technology

The RUDN scientist Dmitry Atyakshin presented innovative molecular histology technology

Dmitry Atyakshin has developed an original combined method of histochemical detection, opening up new opportunities for determining the role of mast cells in the phenotype of the immune landscape and histoarchitectonics of the stromal component of the specific tissue microenvironment.

Dmitry Atyakshin, MD, PhD, Advisor to the Rector on biomedical projects, Director of the Scientific and Educational Resource Center "Innovative technologies for immunophenotyping, digital spatial profiling and ultrastructural analysis" spoke at the XVI International Congress of Histochemistry and Cytochemistry, held in Prague (Czech Republic) from August 28 to 31.

The speaker gave a report "Combined histochemical approach in the evaluation of naphthol AS-D chloroacetate esterase activity of mast cells". The scientist developed an original combined histochemical detection method opening new opportunities to determine the role of mast cells in the phenotype of the immune landscape and histoarchitectonics of the stromal component of the specific tissue microenvironment. The method has received high praise from the Histochemical Society and has been offered publication of the results in the leading journal of molecular histology, Histochemistry and cell biology. A discussion on the development of the university's collaboration on innovative technologies in immunophenotyping and ultrastructural analysis with Stefan Hell, Nobel Laureate in Chemistry "for the creation of high-resolution fluorescence microscopy." Also with leading histochemists from Germany, the Czech Republic, and Japan, which opened up new facets of mutually beneficial integration that contribute to the development of advanced analytical technologies in molecular morphology at RUDN.

Having discovered mast cells in 1978, Paul Ehrlich could not foresee what high interest they would represent in the world scientific community in the future. And this is no accident. Mast cells are one of the key players in the immune landscape of the specific tissue microenvironment. Taking part in regulation of functional phenotype of other cells and extracellular matrix, mast cells regulate spatial architectonics of stromal landscape, state of integrative and buffer metabolic environment, activity of innate and acquired immunity, mechanisms of pathogenesis of most known diseases, including socially significant ones. In translational medicine, mast cells are a promising target for research, since the parameters of their molecular phenotype can not only be used for diagnostic purposes, but also represent a promising pharmacological target.

Development of innovative technologies in assessing the biological activity of immunocompetent cells of the specific tissue microenvironment is in high demand for fundamental research into the mechanisms of pathogenesis and adaptogenesis.

Mast cells represent a promising and highly relevant object of translational research, which is due to their key regulatory positions in the specific tissue microenvironment. In particular, the pathogenesis of cancers, autoimmune diseases, and all conditions accompanied by inflammation and fibrosis is more or less due to the biological effects of mast cells

Mechanisms of intercellular communication ensure the integration of mast cells into the immune and stromal tissue landscapes, providing specificity for the formation of adaptive or pathological states.

The scenario of mast cells interaction mechanisms with immune cells, tumor cells and extracellular matrix both through direct intercellular interactions and through secretion of a wide range of mediators with high biological activity determines the unique properties of the specific tissue microenvironment. Therefore the interpretation of the state of mast cells is in great demand in basic research. However, the key problem until now is still the objectivization of assessment of the state of organ-specific mast cell population, identification of their contribution to morphogenetic and immunogenetic processes taking place at the level of specific tissue microenvironment. The search and development of new histochemical approaches to analyze the state of immunocompetent cells in situ, including the receptor apparatus and mast cell secretome, is one of the urgent tasks of translational research in most priority platforms of biomedical science.

The approach developed in the RUDN University to assess the state of mast cells reveals new facets of the biology of the specific tissue microenvironment and mechanisms of formation of the spatial phenotype of immune and stromal landscapes.

The performed work offers an innovative algorithm for detecting mast cells and studying their interaction with other cells in the regulation of the state of the integrative and buffer metabolic environment of the specific tissue microenvironment. As a result, new fundamental data can be obtained in the study of angiogenesis, oncogenesis, connective tissue remodeling, fibrosis, cell proliferation, intercellular signaling, etc. Thus, the algorithm of histochemical detection technology complements the existing methods of methodological and bionanotechnological capabilities of multiplex immunohistochemistry to reveal selective mechanisms of mast cells participation in the regulation of local homeostasis.

The results of phenotyping the spatial distribution of mast cells in the immune and stromal landscapes of specific tissue microenvironment allow us to identify promising diagnostic and pharmacological targets of pathogenesis of both socially significant and orphan diseases. In particular, mast cells are a source of promising targets for cancer immunotherapy. The effects of the presence of mast cells in the tumor microenvironment are projected onto the possibilities of predicting the outcome of the disease depending on the localization and molecular portrait of the tumor.

The participants of the congress highly appreciated the practical significance of the developed method and recommended its use in basic research.

"The combined method of histochemical analysis of tissue spatial phenotype developed by Dr. Atiakshin et al. opens up new opportunities in studying not only the biology of mast cells but also other cells of the specific tissue microenvironment. The method makes it possible to phenotype the integration of mast cells into the immune tissue landscape as well as the interaction of mast cells with fibroblasts, myofibroblasts and other connective tissue cells. I have no doubt that the development of this histochemical detection method will contribute to a new quality of basic research in molecular histology and increase the efficiency of pathology diagnosis" - Toyoshi Fujimoto, (Juntendo University, Tokyo, Japan, h-index Scopus 51).

In a discussion with Nobel Laureate in Chemistry "for the creation of high-resolution fluorescence microscopy" Stefan Hell (Germany), preliminary agreements were reached on future collaboration in translational research on specific tissue microenvironments using MINFLUX nanoscopy. Throughout 2021-2022, experiments were conducted at the Abberior instruments technology site (Göttingen, Germany) to develop protocols for staining molecular targets of formalin-fixed and paraffin-filled samples, including mast cell secretome components, with specialized Abberior fluorochromes to achieve the best resolving power with Stimulated Emission Depletion (STED) fluorescence microscopy technology.

During the congress, a meeting was held with the regional editors of the journal "Histochemistry and Cell Biology" about the possibility of publishing the results of the RUDN biomedical research in the near and long term.

Based on the results of the research, it is planned to publish an article in a highly rated first quartile journal, as well as to develop cooperation with international partners within the framework of preliminary agreements.

About the event:

The International Congress of Histochemistry and Cytochemistry is one of the oldest forums of fundamental medicine, where breakthrough opportunities of morphological analysis of biomaterial at the molecular, subcellular, cellular and tissue levels of organization are presented, considering the latest advances in chemistry, physics, molecular biology, structural biochemistry, physiology, etc. The periodicity of the event is 4-5 years, the last time the congress was held in 2017 in Antalya (Turkey). More than 200 scientists from scientific and medical organizations of the Czech Republic, Japan, Austria, Hungary, Turkey, Germany, Poland, Italy, France, Malaysia, Switzerland, USA, Spain, Netherlands, UK, etc. attended the congress. Leading researchers in the field of histochemistry and cytochemistry include Toyoshi Fujimoto (Japan, h-index on Scopus 51), Takehiko Koji (Japan, h-index on Scopus 50), Robert Y. Osamura (Japan, h-index for Scopus 44), Bożena Kamińska (Poland, h-index for Scopus 46), Ohad Medalia (Switzerland, h-index for Scopus 38), Christian Mühlfeld (Germany, h-index for Scopus 36), Alev Erisir (USA, h-index for Scopus 32), etc.

On August 31, Dmitry Atyakshin gave an oral report "Combined histochemical approach in assessing naphthol AS-D chloroacetate esterase activity of mast cells" with a presentation of a new histochemical approach to evaluate the biological activity of mast cells. On the same day, Stefan Hell - Nobel Prize Winner in Chemistry "for the creation of high-resolution fluorescence microscopy" (2014), Director of the Max Planck Institute for Biophysical Chemistry (Germany, h-index Scopus 112) gave a keynote lecture.

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