Modern aspects of the use of plasma enriched in soluble platelet factors in the treatment of injuries and diseases of the musculoskeletal system

The review of literature presents the new direction in the treatment of sports injuries and diseases of the musculoskeletal system – using of autologous platelet-rich plasma/plasma enriched in soluble platelet factors (PRP/PORFT). PRP/PORFT reveals anti-inflammatory, analgesic, anticatabolic and regenerative effects after local injection to affected area. Technology of preparation and clinical application of PRP/PORFT were under consideration. There were described the results of clinical studies on PRP/PORFT application in sports medicine and damage of musculoskeletal system. It was shown the clinical efficacy of 2-3 injections of PRP/PORFT into the area of muscle, ligaments, joints injury. Most effective use of PRP/PORFT was shown for therapy of lateral epicondylitis and osteoarthritis. There were no yet evidences for its efficacy in therapy of patients with damaged Achilles tendon. The best clinical effects of PRP/PORFT use was demonstrated in patients with trauma and damage of musculoskeletal system at the initial stages of treatment, and also as a part of rehabilitation courses

Cell technologies in the treatment of rheumatic diseases

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

INTERLEUKIN-2 – AND INTERFERON-ALPHA- INDUCED CHANGES OF PERIPHERAL BLOOD LYMPHOCYTE SUBPOPULATIONS IN CHILDREN WITH ADVANCED MALIGNANCIES, TREATED WITH CHEMOTHERAPY AND WHOLE BODY HYPERTHERMIA

Abstract. The effect of cytokine preparations (Interleukin-2/IL-2/Proleukin and interferon-alpha/IFN-α 2b/ Intron A) on immune cell subpopulations has been studied in the children suffering with advanced malignancies during intensive chemotherapy cycles combined with whole body hyperthermia (thermochemotherapy). It was shown that IFN-α 2b promotes recovery of peripheral lymphocyte counts in the patients. However, no sufficient changes were observed for the lymphocyte subpopulations. Furthermore, more profound lymphopenia along with increased contents of activated (CD25+, HLA-DR+) T cells occurs in a group of children treated with IL-2, as compared to the patients who received IFN-α 2b. Besides that, some differential effects upon the CD4+/CD8+ T-cell ratios were observed in the patients treated with Proleukin or Intron A, with a tendency to increase in CD4+ T-cells for the patients treated with IL-2. It was concluded that differential immunomodulatory mechanisms mediate the effects of IL-2 and IFN-α 2b in the patients with malignancies undergoing combined chemobiotherapy with whole-body hyperthermia

Fourth Generation Phosphorus-Containing Dendrimers: Prospective Drug and Gene Delivery Carrier

Research concerning new targeting delivery systems for pharmacologically active molecules and genetic material is of great importance. The aim of the present study was to investigate the potential of fourth generation (P4) cationic phosphorus-containing dendrimers to bind fluorescent probe 8-anilino-1-naphthalenesulfonate (ANS), anti-neoplastic drug cisplatin, anti-HIV siRNA siP24 and its capability to deliver green fluorescent protein gene (pGFP) into cells. The interaction between P4 and ANS (as the model drug) was investigated. The binding constant and the number of binding centers per one molecule of P4 were determined. In addition, the dendriplex between P4 and anti-HIV siRNA siP24 was characterized using circular dichroism, fluorescence polarization and zeta-potential methods; the average hydrodynamic diameter of the dendriplex was calculated using zeta-size measurements. The efficiency of transfection of pGFP using P4 was determined in HEK293 cells and human mesenchymal stem cells, and the cytotoxicity of the P4-pGFP dendriplex was studied. Furthermore, enhancement of the toxic action of the anti-neoplastic drug cisplatin by P4 dendrimers was estimated. Based on the results, the fourth generation cationic phosphorus-containing dendrimers seem to be a good drug and gene delivery carrier candidate

OUR EXPERIENCE IN APPLICATION OF AUTOLOGOUS BONE-MARROW-DERIVED MESENCHYMAL STEM CELLS FOR THERAPY OF PATIENTS WITH SYMPTOMATIC EPILEPSY

Abstract: an article presented the data on application of autologous multipotent mesenchymal stem cells (MMSCs) from bone marrow for therapy of 10 patients suffering from drug-resistant symptomatic epilepsy. Intravenous injection of 40.0-101.0Ч106 (mean 68.2± 8,48Ч106) MMSCs endolumbal injection of 2.7-8.0Ч106 (mean 6.34±0.72Ч106) neuroinduced MMSCs did non induced in patients unfovarable reactions an complications. Moreover, during 3-11 months of monitoring 5 of 10 patients demonstrated decrease the frequency or disappearance of seizures, severity the incidence of seizures. 2 patients demonstrated increase of cognitive functions, 2 patients – decrease the level of anxiety. We concluded that application of MMSC-base cellular therapy id safe and enable to facilitate seizure status in patients with drug-resistant symptomatic epilepsy

CELL THERAPY OF EPILEPSIA. CLINICAL AND IMMUNOLOGICAL ASPECTS

The aim is to develop and implement a method for the treatment of drug-resistant epilepsy using autologous mesenchymal stem cells and the neuroimaging, immunological and neurophysiological predictors of the brain function.Material and Methods. Twenty patients (12 males and 8 females) with symptomatic drug-resistant epilepsy participated in the study. The patient age varied from 23 to 46 years; and the duration of epilepsy was 7-29 years. Autologous mesenchymal stem cells of the bone marrow were characterized using cultural, morphological, immunological, molecular-genetic, clinical-functional, laboratory, pathopsychological, and neurophysiological methods. The standard parametric and nonparametric statistical tests were used to evaluate the results.Results. The study resulted in producing of cultured autologous mesenchymal stem cells of the bone marrow (AMSCBM) sufficient to conduct 20 courses of cell therapy. In total, 40 transplantation procedures using AMSCBM were performed (20 intravenous and 20 endolumbar injections). Cellularity index in the intravenous inoculate ranged from 39.5 to 110.0 million and that for the endolumbar injection – from 5.1 to 10.0 million with viability not less than 95%. The distribution of AMSCBM by key surface markers (CD105+, CD90+, CD45-, CD34-) matched the criteria of the International Association for cell therapy (ISCT). The cell injections were well tolerated and did not cause any severe adverse effects. To monitor the process of neurogenic differentiation, the expression of the surface markers was determined. In most samples with confirmed neural differentiation, a significant increase in the expression of neuron-specific enolase, nestin and MAR-2 was detected. In patients with symptomatic epilepsy, the most significant deviations from normal values were found for the numbers of cytotoxic and activated cells, natural killer (NK) cells, and T-cells with the NK activity. After a course of cell therapy, a significant decrease in CD4+CD8+, CD3+CD8+, CD3+CD95+, and CD8+CD25+ cells was noted. Also decreased were the numbers of NK cells and T-cells with the NK activity, however, their levels remained relatively high as compared with the control group. Following the treatment, we continued to monitor the patients for 3, 6, and 12 months after the cell administration as well as the patients from the group of comparison.Conclusion. For the first time in the Republic of Belarus, cell therapy in patients with epilepsy was conducted. An intravenous injection of AMSCBM and endolumbar administration of neuro-induced AMSCBM can serve an effective additional therapy of choice in patients with drug-resistant epilepsy