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Immunomodulatory properties of mesenchymal stem cells from patients with amyotrophic lateral sclerosis and healthy donors
Matějčková, Nicole ; Javorková, Eliška (advisor) ; Kanderová, Veronika (referee)
Mesenchymal stem cells (MSC) possess a multilineage differentiation potential and have the ability to regulate reactivity of the immune system. They are usually isolated and expanded from the bone marrow, adipose tissue or umbilical cord. MSC represent promising cell population for the treatment of some severe diseases, such as amyotrofic lateral sclerosis (ALS), due to the combination of regenerative and immunomodulatory properties. The aim of this study is to compare MSC from ALS patients and healthy donors in their phenotype, proliferative activity and mainly their immunomodulatory properties. The assessment of impact of the disease on the properties of MSC is important for their autologous use in clinical trials. In this study we used MSC isolated from bone marrow of 14 ALS patients and 15 patients undergoing mostly orthopedic surgery as control group. We also used MSC stimulated for 24 hours by poinflammatory cytokines. Cells were compared in terms of immunophenotype, differentiation in adipocytes and osteoblasts, metabolic activity, expression of selected genes for immunomodulatory molecules and for inhibition of lymphocyte proliferation. Further experiments were focused on evaluation of immunomodulatory properties of MSC. The effect of MSC on peripheral blood mononuclear cells stimulated...
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Study of the effect of immunological sdjuvants on experimental treatment of HPV-induced tumors by recombinant VACV and DNA vaccines
Gabriel, Pavel ; Němečková, Šárka (advisor) ; Mělková, Zora (referee) ; Reiniš, Milan (referee)
1 ABSTRACT The success of cancer vaccines depends on factors associated with the vaccine, which define the main parameters of effective immune responses such as its size and quality, as well as on factors related with the host, represented by the immunosuppressive mechanisms that allow the tumor to escape recognition by the immune system or negatively influence the function of effector T-cells. Attenuated, non-replicating viruses are at present preferred as VACV for safety reasons. A problem may arise concerning their lack of immunogenicity. Through the deletions of non-essential genes, vaccination vectors are therefore developed based on attenuated rVACV capable of replication, which induce a strong immune response. Genes of various immunological adjuvants (e.g., genes for cytokines and costimulatory molecules) are inserted into the vectors for the purpose of eliminating the influence of the immunosuppressive mechanisms of tumors. The first part of the work describes our study of the influence of vCCI on biological properties of rVACV derived from the Prague strain. Testing of vCCI deletion and insertion mutants expressing tumor associated protein HPV16 E7 has shown that secreted vCCI attenuated the virus in vivo, which correlated with reduced levels of the corresponding CC chemokines in the blood compared...
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Mechanisms of immune tolerance induction in organ transplantations
Brožová, Barbora ; Stříž, Ilja (advisor) ; Hájková, Michaela (referee)
The term transplantation tolerance is considered for a long-term graft survival without the need of immunosuppressive therapy. In experimental models, there are many ways to induce the tolerance but have not been transferred into clinical practice, yet. Currently used pharmacological immunosuppression is designed to allow the body to accept the presence of graft and also to preserve the immune system of the recipient. Results of some studies have shown that doses of immunosuppressive agents can be reduced to a minimum and patients might survive for years without an immunosuppression in few cases. The future of immunological tolerance is associated with the development of biomarkers or the use of mesenchymal stem cells. The aim of this thesis is to summarize current knowledge of mechanisms of immunological tolerance in organ transplantations and try to find prospective targets, which could be directed to further research. Keywords: immune tolerance, organ transplantations, rejection, immunosuppression, immunomodulation
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The use of immunoregulatory properties of mesenchymal stem cells/ and their therapeutic potential
Javorková, Eliška ; Krulová, Magdaléna (advisor) ; Stříž, Ilja (referee) ; Tučková, Ludmila (referee)
Mesenchymal stem cells (MSCs) have the potential to differentiate into various cell types, possess potent immunomodulatory properties and can influence various functions of immune cells. Since the immunomodulatory properties of MSCs can be modified by cytokines, we compered the effect of unstimulated MSCs and MSCs pretreated with interleukin (IL)-1, interferon (IFN)- , transforming growth factor (TGF)- and IL-10 on the development of regulatory T cells (Treg) and T helper 17 (Th17) cells in vitro and on the inflammatory environment in the eye. MSCs can produce significant levels of TGF- and IL-6. These cytokines represent the key factors that reciprocally regulate the development of naive T cells into Treg and Th17 cells. Unstimulated MSCs produce TGF- , but not IL-6, and the production of TGF- can be further enhanced by IL-10 or TGF- . In the presence of IL-1, MSCs secrete significant levels of IL-6, in addition to spontaneous production of TGF- . MSC producing TGF- induced preferentially expression of Foxp3 and activation of Treg lymphocytes, whereas MSCs supernatants containing TGF- together with IL-6 supported ROR t expression and development of Th17 cells. We demonstrated that MSCs and their products effectively control the development of Tregs and Th17 cells in a population of...
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Possibilities of using stem cells for treatment of ocular surface injuries
Kössl, Jan ; Holáň, Vladimír (advisor) ; Drbal, Karel (referee)
Ocular surface defects are one of the most common causes of impaired vision or even blindness. Corneal transplantation is the first choice of the treatment of these defects. If the damage is extensive and includes the limbus, niche of limbal stem cells (LSCs), LSC deficiency (LSCD) occurs and reparation with regeneration of cornea is impaired. The only way to treat LSCD is limbal transplantation or transplantation of autologous LSCs from the healthy eye. In cases of bilateral LSCD there are no autologous LSCs available. The use of allogeneic LSCs is associated with the requirement of systemic or local administration of immunosuppressive drugs which have often negative side-effects and outcomes remain uncertain. The alternative for treatment of ocular surface defects and LSCD is finding a new source of an appropriate autologous stem cell substitute which are e.g. mesenchymal stem cells (MSCs). These cells can be obtained from bone marrow or adipose tissue of the particular patient. MSCs can be easily cultivated ex vivo and can be transferred onto the damaged ocular surface using appropriate scaffold. Here they can differentiate to corneal epithelial cells, have immunomodulatory properties and produce numerous trophic and growth factors. The experiments with MSCs on animal models of mechanically or...
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NK cells and their receptors in immune regulation - possible targets for immunomodulation
Svoboda, Jan ; Fišerová, Anna (advisor) ; Pěknicová, Jana (referee) ; Kročová, Zuzana (referee)
(english) Natural Killers - NK cells play an important role in immune surveilance and regulation either by direct cytotoxicity towards infected, transformed or otherwise damaged cells, or by production of cytokines and chemokines. The resulting response of NK cells is given by the sum of stimulating and inhibiting signals, tranduced by a wide array of receptors. Killer Ig-like receptors KIR2DL4 and LILRB1, which recognize self HLA-G molecules in pregnancy, as well as NKR-P1 receptors, which differ in the number of isotypes, are species-dependent and reduced during phylogenesis. NKG2D, reacting to stress-inducible proteins, and adenosine receptors (AR), which supress the inflamatory reaction, remain evolutionary conserved. The aim of this work was to study the involvement of NK cells and their receptors in several immune disorders and in various species, to provide new insights into their function and posisible immune modulation. We have shown here, that the choice of species in the study of NK cell effector functions may be crucial in some cases. The reaction to glycans, using synthetic GlcNAc-terminated glycomimetics GN8P, exerted opposing effects on NK cell function in humans and C57Bl/6 mice. In humans, the glycomimetic decreased cytotoxic activity of high NKR-P1A expressing NK cells, while in...
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Immunomodulatory effects of macrolide antibiotics
Zemánková, Jana ; Stříž, Ilja (advisor) ; Krulová, Magdaléna (referee)
Macrolide antibiotics are well known not only for their antibacterial properties, but also for their recently discovered anti-inflammatory properties. They are able to significantly suppress destructive and in many cases life-threatening inflammation, an effect which is desired especially in chronic inflammatory diseases. The principle which their act is the modulation of the various components of the immune system. These effects are called "immunomodulatory" and can also include the effect on epithelial cells and their secretory activity, as well as the effect on pathogens which can colonize the airways and contibute to pathogenesis and the emergence of the chronic inflammatory respiratory diseases. This thesis summarizes the most important known mechanisms, by which macrolide antibiotics exert these immunomodulatory effects, and also notes examples of diseases whose treatment is the most clinically significant. Macrolide antibiotics posessing these uniqe anti-inflammatory properties are well tolerated and severe side-effects are rare. However, the most serious risk is the emergence of resistance and that is the main reason why this treatment can not be recommended without reservation. It is up to each doctor to consider the risks and benefits of the treatment in each individual patient.
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The influence of Toll-like receptors on immunomodulatory properties of mesenchymal stem cells
Heřmánková, Barbora ; Krulová, Magdaléna (advisor) ; Indrová, Marie (referee)
Immunosuppressive properties of mesenchymal stem cells (MSCs) offer potential tools for cell-based regenerative therapy and immunotherapy. MSCs express a large number of Toll like receptors (TLRs) recognizing multiple pathogen-associated molecular patterns (PAMPs), which could be found in patients microenvironment and modulate activity of MSCs. TLR ligands could lead to modulation of proliferation, differentiation, immunosuppression, migration, polarization and production of cytokine. This work discusses the effect of TLRs on immunomodulatory properties of MSCs, because there are lots of contrasts in the results about their effect.
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Immunomodulatory properties of mesenchymal stem cells - use in therapy
Pavlíková, Michaela ; Stříž, Ilja (referee) ; Krulová, Magdaléna (advisor)
Mesenchymal stem cells (MSC) are extensively studied mainly due to their feasible clinical application. Therapeutic potential of MSC consists not only of the ability to differentiate into mesenchymal cells, ectodermal and endodermal cell lines, but primarily in their immunomodulatory functions. Due to their effect on immune cells, MSC promote the shift of the inflammatory immune response to antiinflammatory. The ability to suppress inflammation, together with their differentiation potential and antiapoptotic potential on the surrounding cells makes MSC a promising tool for treating serious diseases. This work discusses the effect of MSC on the individual cells of the immune system. It focuses on the description of the effect of MSC in four model cases. These are an experimental autoimmune encephalomyelitis, myocardial infarction, diabetes mellitus and skin graft transplantation. The knowledge of the mechanisms of the interactions between MSC and the cells of the immune system, together with the understanding the effect of specific conditions on MSC is essential for their use in clinical therapy. Keywords: mesenchymal stem cells, immunomodulation, autoimmune diseases, transplantation
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Modulace imunitního systému člověka výživou
Urbišová, Amálie
This bachelor's thesis focuses on nutraceuticals, compounds of functional food, that can be used for treatment or as a prevention of deseases. Structure and important functions of immune system are described in the introduction of the thesis. Following sententious classification diseases, which is connected with immunity of organism. In this chapter it is described food allergy in detail, because its demonstrations are closely connected with nutrition. Thesis demonstrates influence colon intestine microflora on immune system. Next chapter describes problems of functional food, their characteristics and utilization. The important part of the thesis attends to several compounds of functional food, that makes a better immune system. This chapter includes sententious characteristic of nutraceuticals, their functioning on immunity, listing of food sources and recommended daily intake.
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