Репозиторий Университета

Over recent years, mesenchymal stem/stromal cells (MSCs) and their potential biomedical applications have received much attention from the global scientific community in an increasing manner. Firstly, MSCs were successfully isolated from human bone marrow (BM), but in the next steps, they were also extracted from other sources, mostly from the umbilical cord (UC) and adipose tissue (AT). The International Society for Cellular Therapy (ISCT) has suggested minimum criteria to identify and characterize MSCs as follows: plastic adherence, surface expression of CD73, D90, CD105 in the lack of expression of CD14, CD34, CD45, and human leucocyte antigen-DR (HLA-DR), and also the capability to differentiate to multiple cell types including adipocyte, chondrocyte, or osteoblast in vitro depends on culture conditions. However, these distinct properties, including self-renewability, multipotency, and easy accessibility are just one side of the coin; another side is their huge secretome which is comprised of hundreds of mediators, cytokines, and signaling molecules and can effectively modulate the inflammatory responses and control the infiltration process that finally leads to a regulated tissue repair/healing or regeneration process. MSC-mediated immunomodulation is a direct result of a harmonic synergy of MSC-released signaling molecules (i.e., mediators, cytokines, and chemokines), the reaction of immune cells and other target cells to those molecules, and also feedback in the MSC-molecule-target cell axis. These features make MSCs a respectable and eligible therapeutic candidate to be evaluated in immune-mediated disorders, such as graft versus host diseases (GVHD), multiple sclerosis (MS), Crohn’s disease (CD), and osteoarthritis (OA), and even in immune-dysregulating infectious diseases such as the novel coronavirus disease 2019 (COVID-19). This paper discussed the therapeutic applications of MSC secretome and its biomedical aspects related to immune-mediated conditions. Sources for MSC extraction, their migration and homing properties, therapeutic molecules released by MSCs, and the pathways and molecular mechanisms possibly involved in the exceptional immunoregulatory competence of MSCs were discussed. Besides, the novel discoveries and recent findings on immunomodulatory plasticity of MSCs, clinical applications, and the methods required for their use as an effective therapeutic option in patients with immune-mediated/immune-dysregulating diseases were highlighted.

© 2020 Elsevier B.V. Background: The present study focuses on investigation of Intra-articular PDT mechanisms for OA treatment. Also, a search for determination of the most effective dose of chlorin e6 (Ce6) for anti-inflammatory PDT of OA was carried out. Methods: The study was carried out on laboratory animals (11 Chinchilla rabbits, 1 year, 2.5 kg) with a gonarthritis model of post-traumatic OA. According to the instructions for using Photoditazin (Ce6 based PS) for PDT of human oncological and non-oncological diseases, the recommended dose is 0.7–1.2 mg/kg. For studies on rabbits, taking into account the conversion coefficient (3.2), the PS doses of 2.4, 3.2 and 6.4 mg/kg were selected. Fluorescence spectra were measured intra-articular before and after PDT using spectrometer with fiber-optic probe. The intrajoint PDT was carried out using a laser (662 ± 10 nm) and a fiber-optic catheter with a cylindrical diffuser inside a sapphire needle for a uniform distribution of the laser radiation. The immunohistochemical study was carried out by staining the samples with caspase-3. Results: Histological and immunohistochemical analysis showed that the best PS dose for intravenous administration for PDT of rabbit gonarthritis is 3.2 mg/kg. The PS concentration directly in the synovial tissue was 0.5 mg/kg, and this was enough to achieve the most positive results to reduce the caspase-3 level. Conclusion: The caspase-3 level correlates well with other signs of inflammation in the synovial membrane (edema, etc.). Therefore, to assess the PDT effectiveness in the treatment of gonarthritis accompanied by synovitis, it is sufficient to analyze only for caspase-3. The efficacy of PDT with Ce6 showed that 3.2 mg/kg PS dose (1 mg/kg for a human) is the most effective.

© 2020 Elsevier B.V. Background: The present study focuses on investigation of Intra-articular PDT mechanisms for OA treatment. Also, a search for determination of the most effective dose of chlorin e6 (Ce6) for anti-inflammatory PDT of OA was carried out. Methods: The study was carried out on laboratory animals (11 Chinchilla rabbits, 1 year, 2.5 kg) with a gonarthritis model of post-traumatic OA. According to the instructions for using Photoditazin (Ce6 based PS) for PDT of human oncological and non-oncological diseases, the recommended dose is 0.7–1.2 mg/kg. For studies on rabbits, taking into account the conversion coefficient (3.2), the PS doses of 2.4, 3.2 and 6.4 mg/kg were selected. Fluorescence spectra were measured intra-articular before and after PDT using spectrometer with fiber-optic probe. The intrajoint PDT was carried out using a laser (662 ± 10 nm) and a fiber-optic catheter with a cylindrical diffuser inside a sapphire needle for a uniform distribution of the laser radiation. The immunohistochemical study was carried out by staining the samples with caspase-3. Results: Histological and immunohistochemical analysis showed that the best PS dose for intravenous administration for PDT of rabbit gonarthritis is 3.2 mg/kg. The PS concentration directly in the synovial tissue was 0.5 mg/kg, and this was enough to achieve the most positive results to reduce the caspase-3 level. Conclusion: The caspase-3 level correlates well with other signs of inflammation in the synovial membrane (edema, etc.). Therefore, to assess the PDT effectiveness in the treatment of gonarthritis accompanied by synovitis, it is sufficient to analyze only for caspase-3. The efficacy of PDT with Ce6 showed that 3.2 mg/kg PS dose (1 mg/kg for a human) is the most effective.

© 2018, Springer-Verlag GmbH Germany, part of Springer Nature. Abstract: Osteoarthritis (OA), the most common form of arthritis, is characterized by inflammation of joints and cartilage degradation leading to disability, discomfort, severe pain, inflammation, and stiffness of the joint. It has been shown that adenosine, a purine nucleoside composed of adenine attached to ribofuranose, is enzymatically produced by the human synovium. However, the functional significance of adenosine signaling in homeostasis and pathology of synovial joints remains unclear. Adenosine acts through four cell surface receptors, i.e., A1, A2A, A2B, and A3, and here, we have systematically analyzed mice with a deficiency for A3 receptor as well as pharmacological modulations of this receptor with specific analogs. The data show that adenosine receptor signaling plays an essential role in downregulating catabolic mechanisms resulting in prevention of cartilage degeneration. Ablation of A3 resulted in development of OA in aged mice. Mechanistically, A3 signaling inhibited cellular catabolic processes in chondrocytes including downregulation of Ca2+/calmodulin-dependent protein kinase (CaMKII), an enzyme that promotes matrix degradation and inflammation, as well as Runt-related transcription factor 2 (RUNX2). Additionally, selective A3 agonists protected chondrocytes from cell apoptosis caused by pro-inflammatory cytokines or hypo-osmotic stress. These novel data illuminate the protective role of A3, which is mediated via inhibition of intracellular CaMKII kinase and RUNX2 transcription factor, the two major pro-catabolic regulators in articular cartilage. Key messages: Adenosine receptor A3 (A3) knockout results in progressive loss of articular cartilage in vivo.Ablation of A3 results in activation of matrix degradation and cartilage hypertrophy.A3 agonists downregulate RUNX2 and CaMKII expression in osteoarthritic human articular chondrocytes.A3 prevents articular cartilage matrix degradation induced by inflammation and osmotic fluctuations.A3 agonist inhibits proteolytic activity of cartilage-degrading enzymes.

© 2018 American Leather Chemists Association. All rights reserved. Classification, mechanism of action, features of pharmacodynamics and pharmacokinetics, and indications for use of chondroprotectors (drugs promoting the regeneration of cartilage tissue) are presented. Comparative analysis of experimental and clinical studies of main representatives of this group of drug has been performed.

© 2018 Russian Electronic Journal of Radiology.All Rights Reserved. The incidence of hip osteoarthritis and degenerative lumbar spine stenosis increases with the lifespan. The combination of these two conditions is not rare and is known as “hip-spine syndrome” in literature. Due to the similarity of symptoms the main problem is to determine the primary pain generator. Solving this diagnostic problem can lead to proper treatment, surgical or other. Purpose. To provide the literature review of the hip-spine syndrome. Materials and methods. We analyzed articles published on https://www.ncbi.nlm.nih.gov/pubmed during 2004-2018 searching for keywords: «radiographic and clinical hip osteoarthritis» - 1141 results, «lumbar spine stenosis and MRI canal» - 521 results and «hip-spine syndrome» - 35 results, 54 items were chosen due to the objective. Results. Primary source of pain for patients with hip-spine syndrome often remains unclear. The existing diagnostic algorithms are imperfect, about 25% of patients do not feel relief of pain after spine surgery or total hip arthroplasty. Mandatory x-ray examination in case of unknown source of pain is important and can show changes in hip and lumbar spine. That can help to change the way of search for pain generator Conclusion. It is necessary to create new diagnostic algorithms that will be harmless for patients and will be with maximum value for surgeons.

© 2018 Russian Electronic Journal of Radiology. All rights reserved. Purpose. Purpose of the study is to have a detailed examination and investigation of the patient with all the required parameters. Material and methods. Revision knee replacement prosthesis making a difference in treatment outcome. Results. The result after the sleeve operation was uneventful and the patient had no complaints or pain even after a year of surgery. Conclusion. Long term complications are comparatively less when a proper prosthesis is selected for the particular patient operation.

Glycosaminoglycan-peptide complex (GPC) (Rumalon®) is an injectable slow-release anti-inflammatory agent (SRIA) that has complex anti-inflammatory and metabolic effects. GPC has been successfully used in the treatment of osteoarthritis (OA) for several decades. The agent now returns again to Russian clinical practice. Objective: to evaluate the efficacy and tolerability of GPC in patients with knee OA, in whom other SRIAs have been previously ineffective. Subjects and methods. A study group consisted of 104 patients (92.3% women) (mean age, 63.2±8.5 years; body mass index (BMI), 28.5±5.4 kg/m2) with severe joint pain (?40 mm on a 100-mm visual analogue scale (VAS)) and/or the need to regularly use nonsteroidal anti-inflammatory drugs (NSAIDs). All the patients received oral SRIAs in the last 6 months and had no improvement. At baseline, VAS pain intensity was 59.4±13.1 mm; the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain was 227.3±90.8; WOMAC stiffness, 97.9±42.1; WOMAC function, 769.2±326.1; total WOMAC scores, 1095.1±426.6. GPC was used by the standard scheme: 25 intramuscular injections every other day per treatment cycle; the results of treatment were assessed at 8 and 12 weeks by VAS and WOMAC pain scores, needs for NSAIDs, satisfaction with treatment (measured on a 1- to 5-pont scale where 1 = no improvement or deterioration and 5 = the best result). Results and discussion. At 8 and 12 weeks, VAS pain scores decreased by 30.1±18.3% and 36.9±16.9%, respectively; the reductions in WOMAC pain scores were 29.8±16.3 and 38.2±23.4%; WOMAC stiffness scores, 29.2±15.4 and 31.6±17.4%; WOMAC function scores, 27.7±14.7 and 30.6±18.4%; and total WOMAC scores, 27.2±13.5 and 33.6±18.0%. The changes in pain intensity and WOMAC scores were statistically significant in both followup periods (p<0.001). The majority of patients rated their treatment result as good or excellent: 70.2% at 8 weeks and 75.9% at 12 weeks. 31.7% of the patients completely stopped taking NSAIDs at 12 weeks. Two patients were noted to have adverse reactions (pain at the injection site and allergic skin reaction) that did not require treatment discontinuation and completely resolved without consequences after completion of a GPC treatment cycle. Conclusion. GPC is an effective and safe agent for the treatment for OA, as well as in patients with severe OA and inefficiency of oral SRIAs.

Osteoarthritis (OA), the most common form of arthritis, is characterized by inflammation of joints and cartilage degradation leading to disability, discomfort, severe pain, inflammation, and stiffness of the joint. It has been shown that adenosine, a purine nucleoside composed of adenine attached to ribofuranose, is enzymatically produced by the human synovium. However, the functional significance of adenosine signaling in homeostasis and pathology of synovial joints remains unclear. Adenosine acts through four cell surface receptors, i.e., A1, A2A, A2B, and A3, and here, we have systematically analyzed mice with a deficiency for A3 receptor as well as pharmacological modulations of this receptor with specific analogs. The data show that adenosine receptor signaling plays an essential role in downregulating catabolic mechanisms resulting in prevention of cartilage degeneration. Ablation of A3 resulted in development of OA in aged mice. Mechanistically, A3 signaling inhibited cellular catabolic processes in chondrocytes including downregulation of Ca2+/calmodulin-dependent protein kinase (CaMKII), an enzyme that promotes matrix degradation and inflammation, as well as Runt-related transcription factor 2 (RUNX2). Additionally, selective A3 agonists protected chondrocytes from cell apoptosis caused by pro-inflammatory cytokines or hypo-osmotic stress. These novel data illuminate the protective role of A3, which is mediated via inhibition of intracellular CaMKII kinase and RUNX2 transcription factor, the two major pro-catabolic regulators in articular cartilage.

Osteoarthritis (OA), the most common form of arthritis, is characterized by inflammation of joints and cartilage degradation leading to disability, discomfort, severe pain, inflammation, and stiffness of the joint. It has been shown that adenosine, a purine nucleoside composed of adenine attached to ribofuranose, is enzymatically produced by the human synovium. However, the functional significance of adenosine signaling in homeostasis and pathology of synovial joints remains unclear. Adenosine acts through four cell surface receptors, i.e., A1, A2A, A2B, and A3, and here, we have systematically analyzed mice with a deficiency for A3 receptor as well as pharmacological modulations of this receptor with specific analogs. The data show that adenosine receptor signaling plays an essential role in downregulating catabolic mechanisms resulting in prevention of cartilage degeneration. Ablation of A3 resulted in development of OA in aged mice. Mechanistically, A3 signaling inhibited cellular catabolic processes in chondrocytes including downregulation of Ca2+/calmodulin-dependent protein kinase (CaMKII), an enzyme that promotes matrix degradation and inflammation, as well as Runt-related transcription factor 2 (RUNX2). Additionally, selective A3 agonists protected chondrocytes from cell apoptosis caused by pro-inflammatory cytokines or hypo-osmotic stress. These novel data illuminate the protective role of A3, which is mediated via inhibition of intracellular CaMKII kinase and RUNX2 transcription factor, the two major pro-catabolic regulators in articular cartilage.