The article covers the fundamental and applied problems of regenerative biomedicine. As a scientific field, it arose at the end of the XX century and today it is rapidly growing: the mechanisms of cell renewal, tissue regeneration and repair are being elucidated, fundamentally new methods are being developed to combat severe disease caused by damage and loss of vital cells and tissues. The human body is a “self-renewing machine” and during whole life, it produces of tons of cells, thus, demonstrating its strong regenerative potential that can be used in modern medicine. At the Institute of Regenerative Medicine of the Medical Research and Educational Center of Lomonosov Moscow State University preclinical studies and clinical trials of several novel drugs are being carried. Including ones that stimulate the growth of nerve fibers after re-implantation of upper limb parts (finger and palm), and eliminate neurological dysfunctions after hemorrhagic stroke. For the treatment of male infertility, a drug is being developed that stimulates spermatogenesis and restores spermatogenesis. In order to create an antifibrotic drug, a substance secreted by endometrial cells and preventing fibrosis of the tissues of the uterus and other organs, is being identified. The role of navigational receptors (primarily T-cadregin and urokinase receptor) in choosing the direction of tissue growth is being studied.

Within past 30 years of progress since its first clinical use, gene therapy (GT) has gone from an experimental field to the most actively developing area of modern biomedicine. Significant advances during this period were mixed with sharp declines, and this pathway taken together with new ideas and concepts has formed the main milestones which this short review addresses. Analysis of accumulated experience provides directions, makes up for emerging prospects for the development of GT and sets the vector for their implementation. At the same time, we should not forget about the crucial issues of ethics and safety, which are the cornerstones supporting the use of GT in human. This report briefly summarizes the most important events and fundamental provisions that have shaped the modern landscape of GT, outlines its prospects and problematic issues in the field.

The contribution of the Russian histologist and pathologist Alexander Alexandrovich Maximow (1874–1928) to domestic and world science and practice is undoubted and recognized in the world. His research on the pathology of inflammation, the phylogeny of hematopoiesis, and the cyto- and histophysiology of connective tissue, he performed by experimental-histological and cultural methods more than 110 years ago. Their results made it possible to approve the dominance of the monophyletic model of hematopoiesis, to develop the doctrine of the reticuloendothelial system, and to obtain valuable data on the concept of mesenchymal reserve in the tissues of an adult organism.

A.A. Maximow lived a short but extremely busy life. Many of his breakthrough results became the starting point for development by his immediate employees and ideological successors; among them are outstanding names: N.N. Anichkov, N.G. Khlopin, A.A. Zavarzin, V.M. Danchakova and other prominent researchers.

Key achievements of A.A. Maximow are in the foundation of basic approaches to the development of therapeutic cellular technologies of our time.

Aim. The work was aimed to test whether the expression levels of endometrial-specific Hoxa10 and Hoxa11 genes in the mouse uterus change after endometrial injury caused by giving birth, and to suggest a mechanism by which these genes can be upregulated in endometrial stromal cells after injury.

Methods. The study was performed using young (8–10 weeks old) wild-type mice of the C57BL6 line; Hoxa10 and Hoxa11 gene expression in uterine tissues was assessed before delivery, as well as 4 hours and 24 hours after delivery were also used in the work. Hypoxia was modeled in vitro using human endometrial stromal cells by adding 200 mM CoCl2. Inhibition of DNA active demethylation system was performed using the Bobcat339 inhibitor. The level of expression of the Hoxa10 (HOXA10) and Hoxa11 (HOXA11) genes was assessed by real-time PCR coupled with reverse transcription, as well as by Western blotting.

Results. During the first day after birth, both Hoxa10 and Hoxa11 gene expression increases in mouse uterine tissues. In the stromal cells of the human endometrium, during hypoxia modeling, HOXA10 and HOXA11 gene expression increases, and inhibition of the active DNA demethylation system prevents noted increase in the hypoxia model.

Conclusion. We have shown for the first time that the Hoxa10 and Hoxa11 gene expression increases in vivo in the mouse uterus after endometrial damage, and also demonstrated in in vitro experiments that upregulation of these genes in endometrial stromal cells after damage can be caused by hypoxia-induced epigenetic changes associated with the operation of the active DNA demethylation system.

The aim of this study was to investigate the effect of heparin at a concentration of 1 IU/mL on changes in the osteodifferentiation potential of MSC from human adipose tissue under in vitro cocultivation.

Materials and methods. Assessment of the phenotypic profile of MSC from human adipose tissue during cultivation in the presence/absence of heparin was performed by the flow cytometry method using the appropriate dyes according to the manufacturer’s protocol on a MACS Quant flow cytometer after 14 days of cultivation. To evaluate the migration and proliferation potential of MSCs in the presence of heparin, we were using a continuous monitoring electrode system, xCELLigence ® RTCA DP. After cultivation MSCs with heparin for 14 days, the intracellular expression of osteodifferentiation genes was evaluated by real-time PCR. In addition, the differentiation profile of MSCs from human adipose tissue cultured with heparin was evaluated by cytological staining with alizarin red to detect islands of mineralization after 21 days of cultivation. In addition, the amount of growth factors, chemokines, molecules with pro- and anti-inflammatory activity was estimated in the supernatants of the 14-day cultures.

Results. There was a significant decrease ( compared with the control group of the study) in the number of cells with stem markers (CD73, CD90, CD105) on the cell surface of the culture in the MSC + heparin model; increase in proliferative and decrease in migratory activity of MSCs during co-cultivation with heparin; increased levels of relative mRNA expression of genes for osteodifferentiation (ALPL, RUNX2, BMP2, BMP6) and cell adhesion (CD49d); increase in mineralization area in the study model in the presence of heparin after 21 days of cultivation. There was a tendency to increase secretion of growth factor VEGF and pro-inflammatory factor IL -6 in the MSC + heparin model.

Conclusion. The obtained results may serve as a basis for the development of new therapeutic tactics for the treatment of surgical patients undergoing osteosynthesis operations with a high risk of thrombosis.