Search

Osteoarthritis (OA) is the most common disease of the elderly, which is accompanied by pain and damages all tissues of the joint. OA is associated with progressive loss of articular cartilage, sclerotic changes in the subchondral bone and the formation of osteophytes. Cartilage destruction is caused by resorption of the extracellular matrix, which consists mainly of type II collagen and aggrecan proteoglycan. Excessive cleavage of type II collagen in OA is associated with increased synthesis and activity of metalloproteinases and the expression of pro-inflammatory cytokines of interleukin 1β and tumor necrosis factor α. Currently, OA therapy is symptomatic, often ineffective, and in some cases is accompanied by adverse side effects. Therefore, the search for new therapeutic approaches to the treatment of the disease, using modern technological capabilities and knowledge of the metabolic disorders that cause the disease. The review presents new promising methods in the treatment of OA using stem cells and subcellular structures, based on modern knowledge of molecular and cellular mechanisms that are disrupted during development and disease progression.

To date, liver transplantation remains the only effective treatment for patients with cirrhosis. Due to lack of other effective, alternative therapeutic methods, the search and development of new treatment technologies is problem number one. The development of cellular technologies is promising for use in clinical practice. Using this observation as an example, the safety and efficacy of cell therapy technology for prolonged stay on the liver transplant waiting list by a patient with cirrhosis is shown. After intraportal injection of autologous bone marrow-derived mononuclear cells, liver cirrhosis stabilized on the CTP and MELD-Na scales for 22 months of observation, which allowed the patient to wait for an organ and successfully undergo liver transplantation.

Introduction. Nitric oxide (NO) produced by NO synthases (NOS) is involved in the regulation of vital physiological functions. At the same time, NO and NOS are involved in events associated with the tumor process: mutagenesis, proliferation, apoptosis, angiogenesis, etc., exerting a multidirectional effect on the tumor.Objectives – analyze and summarize literature data concerning the role of NO and endothelial NOS (eNOS) in the initiation and progression of tumors, as well as in the inhibition of tumor growth.Materials and methods. In preparing the review, publications of information bases of biomedical literature were used: SciVerse Scopus (538), PubMed (1327), Web of Science (905), Russian Science Citation Index (125).Results. The molecular mechanisms of the action of NO and its derivatives on the initiation and progression of carcinogenesis have been explored. Numerous factors and conditions regulating the activity of eNOS in health and tumor growth have been analyzed. The molecular signaling pathways through which the pro-tumor effects of NO and eNOS, stimulating angiogenesis, lymphangiogenesis, are realized, including through the mobilization of stem cells, are considered.Conclusion. Nitric oxide produced by activated eNOS promotes tumor progression by increasing the proliferation of tumor cells, enhancing the action of pro-angiogenic factors, stimulating angiogenesis, lymphangiogenesis, and metastasis. Selective inhibition of increased eNOS activity may be a promising therapeutic approach aimed at reducing metastasis and tumor growth.

Regenerative medicine represents the field of medicine that aims to grow lost or damaged human organs and tissues. The promise of regenerative medicine focuses on the development of therapy that can regenerate and restore tissues and organs in the human body. The regenerative medicine has the potential of cell renewal in our body, reaching about a kilogram per day, tens of tons in our life. Recent data indicate that a tumor is a tissue that largely repeats the pattern of growth and regeneration of normal tissue. Similar to normal stem cells, tumor stem cells are capable of initiating tumor and its growth. Scientists consider that cancer is a payment for multicellularity [1]. Undoubtedly, this potential must be learned to manage. This is a very difficult problem, since many fundamental mechanisms of cell formation and death have not been fully understood. The development of regenerative medicine as a fundamentally new type of medicine will make it possible not only to control stem cell renewal, but also to prevent malignant transformation. The identification of proteins, micro-RNAs and other factors that regulate the formation and death of cells will identify potential targets for both stimulating endogenous regeneration and controlling cancer.

The aim of the study was to study the role of allogeneic transplantation of hematopoietic stem cells in a patient with the classic course of Hodgkin's lymphoma.Materials and methods. The work was carried out on the basis of the analysis of a clinical case of the clinic of occupational pathology and hematology of the University Clinical Hospital No. Professor V.Ya. Shustov. Examinations, a course of chemotherapy in conjunction with surgery and analysis of the results of a patient with a diagnosis of classic Hodgkin's lymphoma were carried out. Results. An unfavorable prognostic effect of a large amount of previous chemotherapy on overall survival after allogeneic HSC transplantation was revealed. According to the results of PET-CT, the patient achieved PETnegative remission of the disease after all the stages of treatment. Compared to the presented PET / CT scan of 02/07/2020, there is a positive trend in the form of the disappearance of metabolic activity in the 3rd rib on the right, the body of Th 11 and the body of the left ilium.Conclusion. The use of high-dose chemotherapy with hematopoietic stem cell transplantation makes it possible to achieve success in the treatment of patients in cases where the results of chemotherapy are unsatisfactory.

Numerous publications on stem cells and cell therapies have appeared last time. Topics discussed in the literature include the differentiation of exogenous SC into various cell lineages, the replacement of senescent, dysfunctional, and damaged cells. However, in vitro differentiation with the expression of certain markers does not prove replacement of functioning cells in vivo . The application of cell therapies in cardiovascular, hepatic, neurodegenerative diseases, osteoarthritis and diabetes mellitus is discussed in this article. Recent data on COVID-19 are overviewed. Some publications exaggerate successes of cell therapies without giving due consideration to potential adverse effects. In recent years there has been a global expansion of stem cell treatments. In conclusion, therapeutic methods with unproven effects should be applied within the framework of high-quality scientific research shielded from conflicts of interest.

Studies on the regenerative capabilities of tissues have shown that damaged liver can recover using hematopoietic stem cells (HSCs), which are able not only to replace cells in the target organ, but can also deliver trophic factors that support endogenous liver regeneration. There is practically no data on how organ-derived humoral signals involve such morphogenic/trophic cells in circulation. Objective : to investigate the role of non-invasive vibromechanical percutaneous action on the liver in cirrhosis by quantification of CD133+ lymphoid HSCs with specific hepatic marker alpha-fetoprotein (AFP) in patients awaiting liver transplantation. Materials and methods . In order to increase the number of AFP+ part of CD133+ stem lymphoid cells in the blood, the patient’s cirrhotic liver was mechanically activated by transcutaneous microvibration using electromagnetic vibrophones in contact with the skin. This generated mechanical impulses with a 10 μm amplitude and a smoothly varying frequency from 0.03 kHz to 18 kHz and back to within one cycle lasting 1 minute. The amount of AFP+ lymphocyte fraction in the total content of CD133+ HSCs in lymphocytes of potential recipients was monitored by flow cytometry before and during daily 15-minute sonication of the skin zone corresponding to the liver projection for three weeks with eight synphased vibraphones. Results. Sonication of the liver projection zone significantly increased the number of liver-specific CD133+ AFP+ lymphocytes by 2–3 times compared to the baseline values. Repeated similar sonication of the same site after a three-week break showed a statistically insignificant increase from the initial level. With a similar effect on the spinal projection in the control group of waitlisted patients with cirrhosis, there was no increase in CD133+ AFP+ lymphocytes. Conclusion. Mechanical stress prompts the organ to secrete specific humoral signals that provoke the bone marrow to produce additional lymphoid stem cells committed to the liver and recruit them into circulation.

Injuries and degenerative changes of tendons are common damages of the musculoskeletal system. Due to its hypovascular character the tendon has a limited natural ability to recover. For typical surgical treatment, the tendon integrity is restored, but in most cases, there occurs formation of the connective tissue scar resulting in structural and mechanical functionality disruption. The insufficient effectiveness of traditional therapy methods requires the search for alternative ways to restore damaged tendon tissues. This article discusses new effective methods for improving the treatment that base on the use of cellular technologies among which one of the main directions is mesenchymal stem cell application. Due to mesenchymal stem cells, there is a shift from pro-fibrotic and pro-inflammatory reactions of cells to pro-regenerative ones. Stem cells being multipotent and having among other things tenogenic potential are considered a promising material for repairing damaged tendons. The article also describes the sources of progenitor tendon cells including the tendon bundles and pericytes the main markers of which are Scx and Mkx that are proteins of the transcription factor superfamily, and Tnmd that is transmembrane glycoprotein.The growth factors that not only enhance the proliferative activity of mesenchymal stem cells but also promote in vitro tenogenic genes expression as well as the collagen Itype production what is necessary for tendon formation are considered. Along with growth factors, the morphogenetic protein BMP14 is presented, this protein increases themesenchymal stem cell proliferation and contributes directed tenogenic differentiation of these cells, suppressing their adipogenic and chondrogenic potentials.In recent years, mesenchymal stem cells have been used both separately and in combination with various growth factors and different three-dimensional structures providing the interaction with all of the cell types.The issues of the latest 3D-bioprinting technology allowing to make tissue-like structures for replacement damaged tissues and organs are discussed. 3D-bioprinting technology is known to allow acting exact spatio-temporal control of the distribution of cells, growth factors, small molecules, drugs and biologically active substances.

Background. Secondary malignancies in pediatric cancer survivors is an actual problem in modern oncopediatry. Alkylating agents and topoisomerase II inhibitors used for primary tumors treatment, induce secondary acute myeloid leukemia (sAML), which treatment results are unsatisfactory.Objective. By predicating on literature and own data to evaluate clinical and biologic features and therapeutic potential of pediatric sAML.Materials and methods. Six patients (age 7–16 years) with sAML were enrolled the study from June 1998 to December 2016. Follow up until September 2020. Primary tumors, which therapy could induce sAML were acute lymphoblastic leukemia, Burkitt lymphoma, germ cell tumor, osteosarcoma, nephroblastoma.Results and conclusion. From 6 patients, included in the study, 2 are alive (+58 and +67 months after allogenic stem cell transplantation), that match global data. Fludarabine-containing regimens and allogeneic hematopoietic stem cell transplant could be a method of choice for this unfavorable group of patients.

Localized and metastatic tumors are known to lead to the formation of circulating tumor cell (CTC ) clusters in the blood. Currently, there is a heightened interest in the study of molecular and biological characteristics of CTC s. Recent studies have shown the presence of different populations of CTC s in the blood of cancer patients. Some cells are cancer stem cells, some tumor cells undergo epithelial-mesenchymal transition (EMT), and most CTC s do not have features of either stem cells or EMT.The aim of the study was to evaluate the five-year metastasis-free survival rate in patients with invasive breast carcinoma, depending on the presence of various populations of circulating tumor cells in the blood before treatment.Material and Methods. A prospective study included 47 patients with newly diagnosed invasive breast cancer (T1–4N0–3M0), who were treated at Cancer Research Institute, Tomsk National Research Medical Center. The patients aged 31 to 69 years. The presence of different populations of CTC s in the blood of patients before treatment was determined by multicolor flow cytometry on the BD FACS Canto system, using different fluorochrome-labeled monoclonal antibodies to EpCam, CD 45, CD 44, CD 24, and N-cadherin. Five-year metastasis-free survival was evaluated by the Kaplan–Meier method. The differences were considered significant at pResults. The results obtained demonstrated that the presence of both stem-like and non-stem CTC s showing signs of EMT with Epcam+CD 45-CD 44-CD 24-Ncadherin+, Epcam+CD 45-CD 44+CD 24-Ncadherin+, and Epcam(m)- CD 45-CD 44+CD 24-Ncadherin+ phenotypes in the blood of breast cancer patients before treatment reduced the five-year metastasis-free survival rate (p=0.0016, p=0.017 and p=0.011, respectively).Conclusion. Thus, CTC s in the EMT state are informative for liquid biopsy to assess the risk of hematogenous metastasis and can be considered as targets for selection of personalized chemotherapy.

Currently, the classification of eye burns, proposed in 1973 by N.A. Puchkovskaya and V.M. Nepomyashaya. Over the last years, knowledges about the pathophysiology of the burn process has been significantly expanded in the world of ophthalmology. The emergence, in particular, of the concept of limbal stem cells of the corneal epithelium and its application in clinical practice has significantly expanded the possibilities for the diagnosis, treatment, and visual rehabilitation of patients with eye burns. In 1997, M.D. Wagoner proposed a classification of eye burns, in which the grade of burn severity is determined by the degree of damage to the limbal stem cells. Given this approach, the authors conducted a comparative analysis of the classifications of eye burns (of different years) in our country and those that have appeared in the West in recent years. In this regard, the attention of ophthalmologists is offered a new classification of eye burns.

Researches about the origin of epithelial ovarian tumors (EOT) tell about its conception. In particular, the origin of cells from the secondary mullerian system. Also, in the article we examine a new hypothesis that the EOT originates in the epithelium of the fallopian tube (FT) – their contradictoriness and new conception of “precursor escape” which tries to explain the phenomenon of injuries absence of FT by high-grade serous ovarian carcinoma. Carcinogenesis from the FT represents great opportunities for reassessment of clinical data. Also, the article represents the role of stem cells of the surface epithelium of ovaries and FT in EOT carcinogenesis.

Stem/progenitor cells are considered an alternative method of heart failure therapy by promoting regeneration of damaged myocardium in myocardial infarction. Effectiveness of cell therapy depends on the population composition and functional activity of the cell graft, and, in turn, it depends on the conditions of microenvironment. Cultivation of stem/progenitor cells with erythropoietin stimulates proliferative potential causing in vitro resistance to hypoxia, and in vivo stimulation of angiogenesis. We aimed for assessing effects of erythropoietin upon hematopoietic cells. We studied some effects of short-term incubation of bone marrow mononuclear cells (BM-MNCs) in patients with coronary heart disease (CHD) with erythropoietin upon cellular phenotype, cell cycle, apoptosis and their proliferative potential. BM-MNCs were isolated from bone marrow aspirate from patients with CHD in a density gradient, then incubated for 60 minutes with erythropoietin (33.4 IU/ml). Using flow cytometric assay of the total BM-MNCs pool, we have shown there endothelial progenitor cells at different stages of maturation and differentiation, mesenchymal stem cells are. Their total number did not exceed 30%. Short-term incubation of BM-MNCs with erythropoietin reduces expression of CD184 “homing receptor” molecules on CD34+ cells, and causes increase of CD184 on CD31+ cells in the BM-MNCs pool (p < 0.05). In addition, erythropoietin has been shown to cause a delay of CD34+ cells in the resting phase (G0G1), reduce a proportion of cells in the synthetic phase (S) and mitosis (G2/M) (p

Hematopoietic stem cell transplantation (HSCT) from healthy donors is used for blood cancer treatment. Alloreactive graft-versus-host disease (GvHD) is one of the post-transplant detrimental side effects, and the main reason for GVHD after HSCT fully matched for human leukocyte peptide antigens (HLA) presented by HLA molecules on cell surface. These polymorphic peptides, minor histocompatibility antigens (MiHA), arise from any genes, including those expressed at hematopoietic tissues. The latter may lead to the s.c. graft-versus-leukemia effect (GvL), thus preventing relapse of a malignancy. A*02:01 is one of the most frequent HLA alleles for European part of Russia. We assessed frequencies for 20 MiHA-encoded genetic polymorphisms, presented via A*02:01 allele, for plausible bone marrow donors, or hematopoietic stem cells (HSC) from the Donor Registry at Russian National Research Center for Hematology, we have also determined a number of immunogenic mismatches for these 20 MiHA in real donor – recipient pairs. A total of 608 potential donors, 90 donors and 92 recipients were genotyped. Using public data, we have shown that frequencies for MiHA coding genes are most close to appropriate frequencies among the European population. We have calculated probability of MiHA-specific alloimmune response after HSCT: there are chances of 33 and 75% for three or more immunogenic mismatches (IM) for related and unrelated HSCTs, respectively. Real frequencies for immune mismatch in 20 related and 20 unrelated donor – recipient pairs are in accordance with estimated theoretical probabilities. As based on the calculated frequencies, we suggest the LB-NDC80- 1P/A, LB-CCL4- 1T, and HA-1 MiHA to be the most promising minor antigens for targeted cell therapies of hematopoietic tissue malignancies. The data obtained could be used for planning allo-HSCTs in Russian patients.

The potential of heart tissues for self-regeneration is not high and supposedly limited to a small number of the niche stem cells. This makes it extremely important to develop regenerative technologies for the myocardium based on modern techniques, for instance, cell re-programming and 3D bioprinting. However, it is often difficult to differentiate the sensational reports regularly appearing in mass media on “breakthrough” technologies from those that really have practical applications. The article sets out a point of view on the popular technologies for the regeneration of cardiac tissues and myocardium as a whole and reviews their drawbacks. The main problems of the bioprinting approach being actively developed include a low differentiation level with printing by stem cells that does not allow for a full-fledged cardiac tissue without foreign inclusions, as well as technological impossibility, when printing with stem cells, to set up their links with other cells during cell delivery in their corresponding matrix locations. Despite some optimistic reports on the good performance on stem or induced pluripotent cells injections into the myocardial injury zone that were first made public about 20 years ago, nowadays this idea seems rather doubtful, because in the recent years there has been virtually no positive effect of this procedure with a serious risk of complications. As far as growing of heart muscle elements is concerned, the main challenge is the development of the “proper” vascularization of the muscle being grown. At the same time, one has to emphasize practical feasibility of growing relatively small myocardial elements, such as sinus node.

Rheumatic diseases are caused by chronic autoimmune processes that require long-term therapy, which leads to the formation of resistance to the drugs used. The search for new approaches to their treatment in recent years has been enriched with the use of cell therapy methods. They are considered in this review of the literature and include the transplantation of hematopoietic stem cells, mesenchymal stem (stromal) cells, the induction or administration of T-regulatory cells, tolerogenic dendritic cells. The paper discusses methods of obtaining cell products, their safety and clinical use in patients with systemic lupus erythematosus, systemic sclerosis, rheumatoid arthritis, and other rheumatic diseases, and treatment complications. Based on the analysis, the authors give the comparative characteristics of various types of tolerogenic cell therapy for rheumatic diseases and point out their advantages, disadvantages, and the specific features of clinical application.

Erythropoietin (EPO) is mainly used to stimulate erythropoiesis. Its cytoprotective effects upon other cells of the human body and animals were recently shown, in particular, anti-apoptotic effect was observed. EPO effect upon the cells is mediated by interaction with erythropoietin receptor, with a complex forming a heterodimeric bond with β-common chain (CD131). In the present work, we studied the changes in erythropoietin receptor expression, and production spectrum of biologically active molecules in bone marrow mononuclear cells (BM-MNC) of patients with coronary heart disease. The flow cytometric assays showed that short-term incubation of BM-MNC with erythropoietin caused increased expression of the erythropoietin receptors on hematopoietic stem cells and tended to reduce the number of endothelial progenitor cells carrying the erythropoietin receptors. Solid-phase enzyme immunoassay in conditioned media from BM-MNC revealed that long-term (72 hours) exposure of BM-MNC to erythropoietin promoted increased production of IL-1β, PDGF-AB, and Epo, if compared to the basal production level (p < 0.05). Short-term incubation of BM-MNC with erythropoietin (60 minutes) caused a significant increase in the IL-1β, PDGF-AB and CXCL-12 / SDF-1α production levels, as well as significant reduction in the IL-10 production levels compared to the basal levels (p < 0.05).

The article describes the transplantation of hematopoietic stem cells (HSC) in children with severe form of mucopolysaccharidosis type I – Hurler syndrome. This method is recommended for the patients under 2.5 years with a high rate of psychomotor development. According to clinical guidelines, HSC is performed according to traditional high-dose, chemotherapy-based conditioning regimens which provide intense immunosuppression to prevent graft rejection. Currently, it is recommended to use a reduced-intensity conditioning mode. An international multicenter study assessed the long-term outcome in patients with Hurler syndrome and confirmed improvements in life quality and expectancy.

Aim. To determine the incidence of viral, bacterial, and fungal infections in post-transplant period and to assess the prognostic value of infections and their influence on early and long-term results of haploidentical hematopoietic stem cells transplantation (haplo-HSCT). Materials & Methods. Retrospective study included 61 patients older than 18 years with high-risk oncohematological diseases. In the period from 2015 to 2018 all patients received haplo-HSCT. Median follow-up after haplo-HSCT was 12.5 months (376 days, range 6-1202). Patients were divided into two groups. The first group (n = 26) received haplo-HSCT as salvage therapy. It included patients with refractory tumors without remission by the start of haplo-HSCT and patients with early relapses after HLA-matched related or unrelated allo-HSCT. The second group (n = 35) received haplo-HSCT on reaching the optimal pretransplant status (“non-salvage”). Results. The incidence of cytomegalovirus (CMV) reactivation, invasive mycosis, and bacterial infections was 70.4 %, 11.5 %, and 75.4 %, respectively. CMV reactivation and invasive mycosis did not affect either the 35- or the 100-day overall survival (OS). For the first time bacterial infections were stratified based on severity according to Sepsis 3 consensus, which allowed to identify groups of patients with unfavorable prognosis. Severe bacterial infections (sepsis and septic shock) correlated with worse early and long-term results, especially in patients without remission by the start of haplo-HSCT, whereas febrile neutropenia/bloodstream infection did not affect OS. On the whole, mortality associated with bacterial infections was 26.2 %. Conclusion. The main factor affecting early lethality after haplo-HSCT is a severe bacterial infection. The key risk factor is lack of remission by the start of haplo-HSCT. Sepsis 3 criteria can be applied in the period of postcytostatic cyto-penia to identify the group of patients with most unfavorable prognosis (septic shock). The implementation of current infection control methods (genotyping of multiple drug resistant strains and timely determining the strategy of antimicrobial chemotherapy on the basis of the results obtained) into everyday clinical practice can improve the treatment outcomes in this category of patients.

The study objectiveis to investigate the features of subpopulational composition of mobilized hematopoietic stem cells in peripheral blood (PB) and leukocyte concentrates (LC) in adult patients with oncohematological pathology and donors.Materials and methods. In 80 patients with hemoblastoses, expression of CD38, HLA-DR and CD143 (angiotensin-converting enzyme) was measured in PB and LC CD34+CD45low cells. The control group included 10 PB and 14 LC samples from healthy donors. Analysis of PB was performed prior to mobilization of hematopoietic stem cells (HSC) and on the day of leukapheresis prior to HSC collection. LC samples were examined at day 1 after HSC collection.Results.CD143 is expressed on CD34+CD45low cells both prior to mobilization and after it in all patients and donors, but CD34+CD45lowCD143+ cell counts varied depending on diagnosis and mobilization regimen. CD143+ expression on CD34+CD45low cells was significantly higher in patients who received combination of chemotherapy and granulocyte colony-stimulating factor compared to donors and patients with multiple myeloma who received only granulocyte colony-stimulating factor. Along with elevated CD34+CD45low cell count after hematopoiesis stimulation, CD34+CD45lowCD143+ cell counts also increased. It was shown that mobilized HSC almost completely lacks a fraction of early CD34+CD45low progenitor cells not expressing CD38, HLA-DR. Prior to hematopoiesis stimulation among CD34+CD45low cells, CD38+HLADR–cell fractions are prevalent, but after mobilization CD38–HLA-DR+ cell counts increased. No differences between CD34+CD45lowCD143+cell counts in patients with multiple myeloma depending on disease status, sex, age or number of chemotherapy courses prior to HSC mobilizationwere observed.Conclusion. Expression of angiotensin-converting enzyme on CD34+ cells in PB before and after HSC mobilization and in LC was observed. The cell counts varied depending on diagnosis and mobilization regimen.

Multiple myeloma originating from clonal proliferation of plasma cells in the bone marrow is one of the most prevalent hematological malignancies worldwide. The pathogenetic mechanisms of multiple myeloma are far from being elucidated. Nevertheless, it is known that the adipocytes as the prevalent cellular component of bone marrow microenvironment contribute significantly to multiple myeloma growth and progression. The review discloses the recent data on the interactions between bone marrow adipocytes and myeloma cells, hematopoietic stemcells, hematopoietic progenitor cells, mesenchimal stem cells, osteoblasts, osteoclasts, endothelial cells, and cells of immune system. Also, the review places special emphasis on bone marrow adipocyte-produced adipokines, growth factors, cytokines, chemokines, and fatty acids providing the conditions for the preferential growth and migration of malignant plasma cells and contributing to hematopoiesis supression, bone tissue resorption, angiogenesis activation and immunosuppression.

Natural killer (NK) cells are the first population to recover after allogeneic hematopoietic stem cell transplantation. Since the report in 2002 by L. Rugerri et al. showing the effectiveness of NK cell alloreactivity in haploidentical stem cell transplantation, a lot of conflicting studies have appeared about the role of NK alloreactivity in haploidentical and matched unrelated donor transplantations. Current studies demonstrate that the beneficial effects of donor NK alloreactivity are dependent on the transplant protocol – conditioning regimen, graft processing procedure and graft-versus-host disease.

Purpose. To develop a method of producing tissue-engineered constructs (TECs) on the basis of resident mesenchymal progenitor cells (MPC) of the human heart and to assess the effect of TECs transplantation on regenerative processes in the heart using a model of myocardial infarction in rats.Materials and methods. Human resident MPCs were isolated from the right atrial auricle of CAD patients. A similar protocol was used to obtain MPCs from Wistar rats. The MPC immunophenotype was determined by cytofluorometry. Corresponding TECs were obtained on the basis of MPC sheets of human and rats' hearts. Myocardial infarction in rats was induced by ligation of the anterior descending coronary artery followed by TEC transplantation. Euthanasia was performed 30 days after the transplantation. Histological examination of the implant and vascularization cells, morphometric analysis, tracking of the MPC differentiation ability, determination of the content of growth factors by solid-phase ELISA were carried out. Statistical evaluation of the significance of differences was performed using the Statistica 8.0 software package.Results. The analysis of the obtained cell constructs showed that they consisted of several layers of cells interacting with each other by means of connexin 43 and were characterized by good cell viability as a part TECs. The number of vessels in the peri-infarction area under the transplant from the MPC was significantly higher than that in the reference group with signs of differentiation of cardiac MPCs transplanted into endothelial vascular cells.The increased vascularization was combined with an increase in the area of viable myocardial sites and a decrease in LV cavity dilation. Analysis of the cardiac MPC secretion products showed that they produce the most important growth factors and cytokines that regulate angiogenesis and migration of stem cells.Conclusion. The strategy of using epicardial TEC transplantation based on MPC sheets seems to be a rational approach for effective delivery of viable stem/progenitor cells to the damaged myocardium. The use of TEC helps to reduce or temporarily eliminate the effect of factors that contribute to progressive heart dysfunction by local paracrine exposure and activation of the revascularization processes in the affected zone.

Late radiation injury in the form of radiation-induced fibrosis is one of the many complications of radiation therapy. In current literature, pathogenesis of radiation-induced fibrosis is considered from several angles. According to one of the hypotheses, the main cause of pathogenesis of radiation-induced fibrosis is damage of the blood vessels caused by radiation. Another hypothesis insists that radiation causes depletion of specific cell populations in the irradiated area, reducing the number of stem cells (mostly, fibroblasts). Based on our first-hand experience in treating late radiation injures of soft tissues in patients with breast cancer, we measured oxygen perfusion of the skin (TсPО2) in the area of late radiation injury using a transcutaneous monitor TCM 400 (Radiometer, Denmark). The obtained results may give a new insight into pathogenesis of late radiation injures.

Aim. Comparative efficacy analysis of autologous hematopoietic stem cells (HSC) prior to auto-HSCT in patients with lymphoproliferative disorders (LPDs) and multiple sclerosis (MS). Materials & Methods. The trial included 237 patients: 103 LPD and 134 MS patients. In 225 patients HSC mobilization involved only colony-stimulating factors (CSFs), in 12 patients chemotherapy (cyclophosphamide, etoposide) was combined with CSFs. On the intended date of cytapheresis all the patients were tested for CD34+ marker expression. Сytapheresis followed in the patients with CD34+ count more than 0.01 x 106/mL. Results. In 23 (22 %) LPD patients CD34+ count was too low for auto-HSCT (‘collection failure group'). Within this group 19 patients received CSF mobilization, and 4 patients received chemotherapy + CSF. Plerixafor was administered in 5 patients, in 4 of them a repeated mobilization also failed to collect enough cells. In 80 LPD patients the number of mobilized and collected CD34+ cells was sufficient for auto-HSCT (‘collection success group'). Within this group 77 patients received auto-HSCT, 74 patients were treated with CSF mobilization, 6 patients received chemotherapy + CSF, and in 11 patients plerixafor was administered. Median total number of CD34+ cells in the ‘collection success group' was 2.7 x 106/kg. All 134 MS patients had enough CD34+ cells for auto-HSCT. All of them received CSF mobilization. Median total number of CD34+ cells in the MS group was 2.34 x 106/kg. Potential risk factors for HSC mobilization failure in LPDs were evaluated. They included age, gender, prior radiotherapy, number of antitumor treatment lines prior to auto-HSCT, clinical response prior to auto-HSCT (complete/partial remission or stabilization), and HSC mobilization regimen. These factors with the exception of gender were not associated with mobilization failure parameters. The worst mobilization outcomes were reported in male patients. Conclusion. In 22 % of LPD patients the planned high-dose chemotherapy and auto-HSCT failed due to insufficient counts of autologous CD34+ cells in apheresis product. Male gender can be considered to be a prognostic factor of mobilization failure in LPDs.

The aim of the study is to present a successful case in treating primary cutaneous anaplastic large cell lymphoma (PCALCL) occurring with common lesions of the skin and lung tissue.Materials and methods. For the verification of the diagnosis in a patient with three types of skin elements (spot, thin plaque with and without ulceration), differential diagnosis was performed between ulcerative pyoderma gangrenosum, PCALCL, large-cell transformation of mycosis fungoides, and secondary skin lesions under the nodal ALK-negtaive ALCL. A complex of studies, including histological, immunohisto - chemical, cytogenetic studies of skin tumor biopsy, allowed the verification of the PCALCL diagnosis. For the treatment of the patient, intensive induction chemotherapy was used followed by high-dose consolidation and autologous transplantation of hematopoietic stem cells.Results. The selected treatment tactics allowed a long-term complete remission of the disease to be achieved in a patient from the poor prognosis group.Conclusion. An algorithm for the differential diagnosis and tactics of treating is presented for a patient with primary anaplastic large cell lymphoma with a widespread skin lesion and extradermal foci.

Аутологичная трансплантация гемопоэтических стволовых клеток (аутоТГСК) – метод эффективного лечения рассеянного склероза (РС), позволяющий замедлить инвалидизацию и улучшить качество жизни больных. Иммуносупрессивная терапия часто сопровождается развитием инфекционных осложнений, что требует тщательного инфекционного контроля. В настоящей статье представляем случай развития инфекционного осложнения, вызванного редко встречающимся возбудителем Weissella confusa., Autologous transplantation of hematopoietic stem cells (autoHSCT) is a method of effective treatment of multiple sclerosis (MS) that can slow the degree of disability in patients and improve their quality of life. Immunosuppressive therapy is often accompanied by the development of infectious complications, such as sepsis, so the careful infectious control is very importartant. The article presents a case of sepsis caused by a rare pathogen of Weissella confuse., Вестник Национального медико-хирургического Центра им. Н.И. Пирогова, Выпуск 1 2021, Pages 158-160

Введение. Наблюдения за больными COVID-19 показали развитие коагулопатии на фоне тяжелой инфекции, вызванной SARC–CoV-2. Патогенетические механизмы влияния SARC–CoV-2 на систему гемостаза в настоящее время активно исследуются, однако для практического здравоохранения крайне актуальным является поиск маркеров активации системы свертывания крови с целью ранней профилактики тромбоэмболических осложнений у пациентов с COVID-19. Цель исследования: определить количество микрочастиц, отделяющихся от клеток крови, у больных COVID-19 и здоровых индивидуумов и проанализировать корреляцию числа микрочастиц с лабораторными и клиническими характеристиками пациентов. Материалы и методы. Обследованы 10 пациентов с COVID-19, госпитализированных в ФГБОУ ВО СЗГМУ им. И. И. Мечникова Минздрава России в период июнь-июль 2020 г., контрольную группу составили 12 сотрудников ФГБОУ ВО СЗГМУ им. И.И. Мечникова Минздрава России без признаков острого респираторного заболевания, без сердечно-сосудистых и тромбоэмболических эпизодов в анамнезе. У всех обследованных выполнен клинический анализ крови, исследованы маркеры активации и воспаления, а также измерено количество внеклеточных микровезикул — экзосом на проточном цитометре. Результаты. У пациентов с COVID-19 по сравнению с контрольной группой наблюдалось увеличение относительного количества нейтрофилов и снижение тромбоцитов. Такие маркеры как фибриноген, С-реактивный белок, ферритин, интерлейкин-6 и лактатдегидрогеназа значительно превышали верхнюю границу референтных значений. При этом количество экзосом оказалось значимо выше у пациентов с COVID-19 по сравнению со здоровыми лицами (% позитивных событий) — 93,2 [88,7–96,5] против 56,2 [50,5–73,5] соответственно (p = 0,00001) и коррелировало с относительным уровнем нейтрофилов. Среди проанализированных экзосом преобладали микрочастицы тромбоцитарного и лейкоцитарного происхождения. Заключение. Увеличение количества внеклеточных микрочастиц у больных COVID-19 может быть использовано как маркер активации гемостаза и повышенного риска тромботических осложнений на фоне инфекционного заболевания., Background. The monitoring of COVID-19 patients showed the development of coagulopathy in the context of severe infection caused by SARC–CoV-2. The pathogenetic mechanisms of SARC–CoV-2 influence on hemostasis are currently being actively examined, but the search for markers of the blood-clotting system activation for early prevention of thromboembolic complications in patients with COVID-19 is highly relevant for the practical health care. Objectives: to analyze the number of microparticles that separate from blood cells due to the hemostasis activation in COVID-19 patients and in healthy donors and to analyze the correlation between microparticles number and laboratory and clinical characteristics of patients. Patients /Methods. The study included 10 patients with COVID-19 who were hospitalized in Mechnikov North- Western State Medical University in June- July 2020; the control group consisted of 12 employees of Mechnikov North- Western State Medical University without signs of acute respiratory disease, without cardiovascular and thromboembolic episodes in the history. All patients and individuals in the control group had their blood clinically tested on a 5-Diff hematological analyzer, markers for activation and inflammation were examined, and the number of extracellular microvesicles (exosomes) was measured on the flow cytometer. Results. Patients with COVID-19 had an increase in the relative amount of neutrophiles and a decrease in platelets compared to controls. Markers such as fibrinogen, C-reactive protein, ferritin, interleukine-6 and lactate dehydrogenase significantly exceeded the upper reference limit. The number of exosomes was significantly higher in patients with COVID-19 compared to healthy controls (% of positive events) — 93.2 [88.7–96.5] vs. 56.2 [50.5–73.5] respectively (p = 0.00001), and correlated with the relative level of neutrophiles. Among the exosomes analyzed, platelet and leukocyte microparticles prevailed. Conclusions. The increase of extracellular microparticles in COVID-19 patients can be used as a marker of hemostasis activation and increased risk of thrombotic complications in the context of severe infectious disease., Тромбоз, гемостаз и реология, Выпуск 4 2020

Aim. To establish correlation between CD34+ autologous hematopoietic stem cell (HSC) count and colony-forming units (CFU) in the same peripheral blood apheresis product samples before and after cryopreservation in multiple myeloma and lymphoma patients, and to assess clinical value of these parameters. Materials & Methods. Cell samples of peripheral blood cyta-pheresis product and cell cultures were studied before and after cryopreservation in 32 multiple myeloma and 25 lymphoma patients who underwent autologous HSC transplantation. The material was analyzed using culture technique and flow cytometry. Results. The paper provides information on the relationship between CD34+ HSC count obtained by flow cytometry, and CFU in cell culture obtained by cytapheresis of the same peripheral blood samples. A direct correlation was confirmed between CD34+ count and all the CFUs before and after cryopreservation in lymphoma patients. Correlation between CD34+ count and granulocyte-macrophage CFUs was revealed in multiple myeloma and lymphoma patients before cryopreservation. Conclusion. The parameter of colony-forming capacity used for the assessment of the functional HSC was shown to be equally reliable criterion for condition evaluation of autotransplant proliferative pool than CD34+ cells. Both methods should be applied for qualitative and quantitative evaluation of an autotransplant for multiple myeloma and lymphoma patients.

The purpose of the study : determination of content of circulating endothelial cellsin umbilical cord blood in orderto assessthe regenerative potential of the endothelium in newborns. 29 newborn babies were examined: 18 pre-term infants (gestational age 30–35 weeks) and 11 full-term infants (gestational age 38–41 weeks). Determination of the number of circulating endothelial cells was determined in mixed umbilical cord blood of all children their phenotyping was carried out by cytofluorometry method using fluorochromes-labeled monoclonal antibodies. Circulating endothelial cells were defined as CD45–, CD133+, VEGFR2, CD34–, endothelial progenitor cells were defined as CD45–, CD133+, VEGFR2+, CD34+. It was revealed that in umbilical cord blood of pre-term infants was decreased both the total number of circulating endothelial cells and endothelial progenitor cells compared to full-term infants. Moreover, in preterm infants was observed higher percentage of endothelial progenitor cells, rather than mature endothelial cells. In blood of full-term infants was observed higher percentage of mature endothelial cells compared to endothelial progenitor cells and their number increases with increasing birth weight of the newborn. The decrease in the number of endothelial progenitor cells in pre-term infants is associated with impaired endothelial function. CD45–CD133+VEGFR2+CD34+ cells are involved in reparation of damaged endothelium and reduction in their number in the blood reflects the reduction of its regenerative potential.

Introduction. Ocular surface diseases related with limbal epithelial stem cells dysfunction were united in term “limbal stem cell deficiency” (LSCD). For experimental study of the regenerative processes and evaluation of the success of new LSCD treating methods LSCD model is required. Various LSCD models were proposed in the experiment to study: mechanical, thermal, chemical, medicamental. The main lack of these models were the relative high cost and complexity of execution. The mechanical model allows for the guaranteed removal of tissues containing LESCs, and therefore seems to be the most acceptable. We offered a modification of the mechanical LSCD model in rabbits. Purpose to create a standardized modification of the mechanical limbal stem cell deficiency model in the experiment. Material and methods. The experimental study was performed in 10 mature Chinchilla rabbits (20 eyes) with an average weight 2.5–3.5 kg. With the local anesthesia, after a 40-second application of the filter paper impregnated with 20% ethanol, the corneal epithelium was removed. With microsurgical diamond blade we metered limb portion of 4 mm width, 0.2 mm deep, and it was removed along the 360° rim. Results. On the 30th day we discovered corneal opacity and neovascularization with conjunctival pannus extending to the optical zone of the cornea. Histological examination revealed tissue edema, inflammatory infiltration, and newly formed vessels. In some places, thinning of epithelium to one row of flattened cells was observed. The Bowman membrane was deformed and practically not detected. Histological examination and impression cytology confirmed the presence of goblet cells in the corneal epithelium. Conclusions. Our modification of the mechanical limbal stem cell deficiency model is devoid of the main lacks of previous models, such as the high cost and complexity of execution, provides intraoperative limbal tissue resection depth control and excludes the possibility of the eye perforation. It is effective, universal, standardized and available for widespread use.

The information given in the scientific literature sources about the transplantation of autologous adipose tissue (AAT) enriched with stem cells (SC) in cases of breast shape and volume correction (in both aesthetic indications and elimination of postoperative deformities) is characterized by versatile results. This circumstance promotes the purposeful study about the possibilities of modern surgical technologies in use of mesenchymal SC (MSCs) of autologous adipose tissue in cases of mammoplasty. The information on the basic techniques of mesenchymal SC isolation from the AAT has been analyzed. The data of cytological criteria were studied separately that allow to relate this biological substance to the SC. Technical features of stem cells transplantation derived from the autologous adipose transplant in cases of mammoplasty are demonstrated. According to opinion among the competent researchers, elimination of postoperative deformities using cellular technologies is a promising scientific direction of medicine.

Modern first-line therapy programs can cure about 80% of patients with classical Hodgkin lymphoma at any stage of the disease, but 10-30% of patients is refractory and need to continue treatment. The treatment standard for relapsed or refractory forms of classical Hodgkin lymphoma is the second-line chemotherapy with high-dose consolidation under the protection of autologous blood stem cells, but the efficacy of such therapy does not exceed 50% for the entire group of refractory patients. The release of target drugs specific for Berezovsky-Reed-Sternberg tumor cells opens up new prospects for the treatment of classical Hodgkin lymphoma. The article reviews the studies of the use of a new target drug Brentuximab Vedotin for the treatment of relapsed and refractory forms of classical Hodgkin lymphoma.

Introduction. Diseases of peripheral arteries constitute important medico-social problem, what demands elaboration of new types of therapy, and application of autologous stem cells in particular. Objective. To study a morphofunctional state of the lower extremities in rabbits, in whom chronic critical ischemia of the lower extremities tissues was simulated and a culture of adipose-derived stem cells (ADSCs), оbtained from their tissue, was applied. Маterials and methods. In the investigation 18 rabbits-females, divided on 3 groups, were studied: pseudooperated (І), оperated, to whom isotonic solution of NaCl was injected (ІІ), and оperated, to whom ADSCs was injected (ІІІ). Моrphofunctional state of pelvic extremities was estimated in accordance to the duplex flowmetry data, and functional tests and morphological investigation were conducted. Results. In laboratory animals of group ІІІ a partial restoration of the pelvic extremity function and improvement of the muscle tissue state was observed, what was absent in laboratory animals group ІІ. In group ІІІ the arrest of the necrotic processes progress and partial epithelization of trophic ulcers were noted. Conclusion. Application of ADSCs while simulation of chronic critical ischemia of tissues in rabbits have promoted restoration of the pelvic extremity function, demonstrated by qualitative and quantitative changes in morphofunctional indices in 5 weeks after injection of stem cells. Кeywords: chronic critical ischemia of the lower extremities tissues; diseases of peripheral arteries; ADSCs; еxperiment.

Background & Aims. The aim of the study was to evaluate the efficacy and safety of azacytidine and decitabine prior to allogeneic hematopoietic stem cell transplantation (allo-HSCT) in acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia and juvenile myelomonocytic leukemia. Materials & Methods. The research included 62 patients who received hypomethylating agents (HMA) prior to allo-HSCT. The median age was 28 years (range from 1 to 68 years), the study population consisted of 27 (43.5 %) women and 35 (56.5 %) men. Results. The overall response (complete + partial remission) was observed in 42 % (n = 26) of cases. At the time of allo-HSCT no disease progression was observed in 41 (66 %) patients. The multivariant analysis showed the overall survival (OS) statistically significantly increased with the graft retention (hazard ratio [HR] 0.002; 95% confidence interval [95% CI] 0.001–0.74; p = 0.03), and also with the administration of HMA after allo-HSCT (HR 0.24; 95% CI 0.08–0.67; p = 0.007). The response (stabilisation, partial or complete remission) due to HMA administration prior to allo-HSCT (HR 6.4; 95% CI 0.75–54.0; p = 0.08) was associated with improved OS. The event-free survival (EFS) was significantly higher with the response to azacytidine and decitabine at the time of allo-HSCT (HR 38.9; 95% CI 1.3–1198.0; p = 0.03) and with the graft retention (HR 0.02; 95% CI 0.005–0.1; p = 0.001). In patients with MDS compared with AML (HR 2.3; 95% CI 0.9–22.0; p = 0.08), there was a tendency to EFS improvement. Progression-free survival rates were higher in patients with a number of blast cells in the bone marrow less than 31 % at the time of diagnosis (HR 1.1; 95% CI 1.1–9.9; p = 0.01). Conclusion. The use of azacytidine and decitabine prior to allo-HSCT allows to safely control the tumor mass in patients with MDS and to maintain the achieved remission with AML. In patients with a response to HMA, the best OS and EFS values are seen after allo-HSCT.

Natural killer (NK) cells represent a lymphocyte subpopulation which is capable of contact cytolysis of virus-infected cells and tumor cells, being a source of cytokines which stimulate other immune cells and promote immune response. NK cell differentiation is connected with a consequent acquisition of specific NK cell receptors by stem cells and formation of functional characteristics inherent to natural killer cells. The aim of this review was to describe the CD56dim and CD56bright populations of NK cells in the course of their differentiation. The authors describe NK surface receptors and expression of transcription factors at various steps of the NK differentiation. We present comparative characteristics of data concerning cytokines and cellular microenvironment influence upon NK cell differentiation, and examine a phenomenon of existing memory-like NK cells. Uterine NK cell differentiation is of special interest, since these cells represent a special NK cell population which prevails among decidual lymphocytes during pregnancy and participates in the process of placental formation and development. This review considers some features of uterine NK cell differentiation, taking into account a possibility of formation of this NK cell population from both peripheral blood NK pool, and in situ proliferation. Moreover, functional studies of the uterine NK cells allow to get closer to understanding the role of NK cells during pregnancy and abnormality of utero-placental bed regulation by NK cells in cases of pregnancy failure.

Цель оценка влияния препаратов суммарной РНК лимфоидных клеток на уровень глюкозы в крови при экспериментальном аллоксановом диабете. Методика. Работа выполнена на 68 белых беспородных крысах обоего пола массой 180220 г. Для моделирования аллоксанового сахарного диабета 1 типа животным однократно подкожно вводили полный адъювант Фрейнда в дозе 0,5 мл/крысу. Через 24 ч (на фоне 24часового голодания, при свободном доступе к воде) однократно подкожно вводили препарат аллоксан тригидрат ( La Chema , Чехия) в дозе 200 мг/кг (4 раствор в 0,9 NaCl). Для предотвращения фатального кетоацидоза, начиная с 3х сут после введения аллоксана, все крысы получали базисную инсулинотерапию. В экспериментах использовано 8 разновидностей препаратов суммарной РНК: из лимфоидных клеток селезенки, из костного мозга и хвостовой части поджелудочной железы интактных крыс (РНКс1, РНКкм1 и РНКп/ж, соответственно) из лимфоидных клеток селезенки крыс, подвергнутых кровопусканию в объеме 2 от массы тела за 17 ч до выделения РНК (РНКс2 с индуцированной повышенной морфогенетической активностью) из лимфоидных клеток селезенки и тимуса крыс, подвергнутых кровопусканию в объеме 2 от массы тела за 96 ч до выделения РНК (РНКс3 и РНКт3, соответственно, с высокой ингибирующей морфогенез активностью) из лимфоцитов периферической крови здорового человека (РНКлпкч), а также из стволовых клеток стромы пупочного канатика человека. Результаты. Показана возможность восстановления функции инсулярного аппарата и стойкой нормализации уровня глюкозы в крови крыс с экспериментальным аллоксановым диабетом 1 типа. Установлено наличие корригирующей способности аллогенных и ксеногенных препаратов суммарной РНК, выделенной из лимфоидных органов крыс и лимфоцитов периферической крови человека, а также из мезенхимных стромальных клеток пуповины человека, в отношении уровня глюкозы крови у крыс. Продемонстрирован различный вклад препаратов суммарной РНК, полученной из разных лимфоидных органов и стволовых клеток, в восстановлении нормального уровня глюкозы в крови животных. Установлено, что указанные препараты действуют на разные тканимишени в процессе восстановления функции инсулярного аппарата. Заключение. Полученные данные свидетельствуют о принципиальной возможности эффективного лечения сахарного диабета 1 и 2 типов. Доказана эффективность неинвазивного интраназального введения аллогенных и ксеногенных препаратов суммарной РНК лимфоидных и стволовых клеток. Полученные результаты ставят вопрос о необходимости разработки более адекватной экспериментальной модели, а также о перспективности поиска подходов к персонифицированному индивидуальному лечению этой патологии с учетом особенностей ее развития в каждом конкретном случае., Aim. To study the effect of total RNA from lymphoid cells on blood glucose in experimental alloxan diabetes mellitus (DM). Methods. The study was conducted on 68 white mongrel rats of both sexes weighing 180220 g. Alloxan DM was modeled with full Freunds adjuvant (0.5 ml/rat). After 24 h of fasting with free access to water, a single dose of alloxan trihydrate (La Chemas, Czeck Republic) was injected subcutaneously (200 mg/kg as a 4 solution in saline). All rats received basis insulin therapy starting from day 3 of the alloxan injection to prevent fatal ketoacidosis. Eight types of total RNA were used: from splenic lymphoid cells, bone marrow, and caudal part of the pancreas of intact rats from splenic lymphoid cells of rats after blood withdrawal (2 of body weight 17 h prior to RNA isolation) (RNA after induction of increased morphogenetic activity) from splenic and thymic lymphoid cells of rats after blood withdrawal (2 of body weight 96 h prior to RNA isolation) (RNAs with high morphogenesisinhibiting activity) and from peripheral blood lymphocytes and umbilical cord stromal stem cells of a healthy human. Results. The study showed a possibility for functional recovery of the insular apparatus and stable normalization of blood glucose level in rats with experimental alloxan DM, a model of clinical type 1 DM. Allogenic and xenogeneic total RNAs isolated from rat lymphoid organs, peripheral blood lymphocytes, and mesenchymal stromal cells of human umbilical cord were able to correct the blood glucose level in rats. Total RNAs isolated from different lymphoid organs and stem cells differently contributed to normalization of blood glucose in rats. These total RNAs were shown to influence different target tissues during restoration of the insular apparatus function. Conclusion. The study showed a principle possibility of effective therapy for types 1 and 2 DM and demonstrated the efficacy of noninvasive intranasal administration of allogenic and xenogeneic total RNAs from lymphoid and stem cells. These results indicated a need for developing a more relevant experimental model and offered a promising outlook for individualized treatment of this disease with due account of its peculiar features in each specific case. The study was conducted as a part of the Program for Basic Research of State Academies of Science in 20132020 on Development of Cell Models for Molecular Processes in Organs and Tissue (V.N. Orekhovich Research Institute of Biomedical Chemistry) and the complex Research Work 01201354257 on Regulation of Hemopoietic and Nonhemopoietic Functions of Bone Marrow Cells in Experiment and Clinic (Sounth Ural State Medical University)., №3 (2019)

Приведены результаты клинических исследований по применению аллогенных адипогенных мезенхимальных стволовых клеток (АМСК) при лечении ожогов кожи II–III степени (по МКБ 10). Клиническая оценка эффективности биомедицинских клеточных продуктов со стволовыми клетками КККПТМ (гель для местного применения) и ММСК™ (для инъекционного введения) демонстрирует их способность оптимизировать репаративную регенерацию в зоне ожоговых поражений. Аппликация геля с АМСК сокращает продолжительность периода эпителизации пограничных (дермальных) ожоговых поражений в 2,2–2,4 раза, при этом окончательный срок заживления таких ран сокращается в 2 раза (p, This is the results of clinical studies of the use of allogeneic adipogenic mesenchymal stem cells (AMSC) in the treatment of skin burns II–III degree (ICD-10). Clinical evaluation of the efficacy of biomedical cell products with stem cells CCRTM (topical gel) and MMSC™ (for injection) demonstrates their ability to optimize reparative regeneration in the area of burn injuries. The application of the gel with AMSC reduces the duration of epithelialization period of borderline (dermal) burn lesions by 2,2–2,4 times, wherein the final healing period of such wounds shortened by 2 times (p, №4 (2019)

Objective. To study the morphometric characteristics of eutopic and ectopic endometrial basal cells in patients with endometriosis and without. Material and Methods: The study involved 76 women aged 17 to 42 (average age was 28.97 ± 5.34 years). The main group consisted of 61 women with ovarian endometriosis, control group - 15 patients with infertility, not related to endometriosis. Results. Morphometric evaluation basal endometrial cells revealed that in patients with endometriosis compared with patients without a thickness of 1.25 times lower than the cytoplasmic membrane thickness gland - 1.5 times the thickness of the nuclear membrane - 1.2 times higher average brightness - 1.2 times lower average density - 1.2 times higher. When comparing eutopic and ectopic endometrial cells in endometriosis patients with the following data: the core area is 1.7 times higher in the eutopic endometrial cells, secretory thickness of the cage 2-fold higher in the eutopic endometrial cells, cytoplasmic membrane thickness is 1.3 times higher eutopic endometrial cells, the average density is 1.2 times higher in the cells of ectopic endometrial average brightness 1.19 times higher in eutopic endometrial cells. Conclusion. The results of our work have demonstrated the obvious statistically significant differences in the morphometric analysis of the basal epithelial cells of eutopic between female patients with endometriosis without it. Consequently, not only stem cells from different ectopic foci localization eutopic cells, but the cells themselves and the basement membrane, which are located on mesenchymal stem cells on their morphometric characteristics are distinct and different from endometrial cells without endometriosis patients.