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The effect of environmental factors on mesenchymal stem cells
Hlávka, Jakub ; Krulová, Magdaléna (advisor) ; Vištejnová, Lucie (referee)
Mesenchymal stem cells (MSCs) have the potential to be a valuable therapeutic tool due to their capacity for differentiation and immunomodulation. However, in order to ensure their efficacy in clinical applications, it is necessary to gain a comprehensive understanding of the factors influecing their properties. This bachelor thesis investigates the influence of environmental factors, including physical activity, temperature and light exposure, on MSCs functionality. Additionally it desribes the underlying mechanisms involved in the action of these factors. Finally, it evaluates the theoretical implications of exploiting environmental cues to enhance MSCs properites. An understanding of how environmental conditions shape MSCs behavior is essential for optimising their therapeutic potential and advancing regenerative medicine strategies. Key words: mesenchymal stem cells, environmental factors, physical activity, temperature, light
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Modulation of mitochondrial transfer by influencing mesenchymal stem cells
Fráňová, Markéta ; Krulová, Magdaléna (advisor) ; Rohlenová, Kateřina (referee)
Mesenchymal stem cells (MSCs) have the ability to modulate the immune response. They use several mechanisms to affect the function of immune cells, and mitochondrial transfer is one of them. Recieving mitochondria from MSCs induces metabolic changes in immune cells, thereby promoting their shift to an anti-inflammatory phenotype. Due to their properties, MSCs have a potencial to be used in therapies, for example in a treatment of autoimmune diseases. The problem of MSCs-based therapies is their low efficacy, mainly due to the high mortality of stem cells after transplantation. In order to achieve at least some effect, the large number of cells is needed for application. The required number of cells can be obtained only by in vitro expansion. However, a long-term culture has a negative impact on MSCs and their immunomodulatory properties. Enhancing MSCs function could increase the efficacy of MSCs-based therapies. The aim of this thesis was to determine whether mitochondrial transfer can be modulated by stimulation of MSCs with selected factors. MSCs were treated with rapamycin, insulin-like growth factor 1 (IGF-1), interferon gamma, or oligomycin. Then the effect of these factors on mitochondria and their transfer to immune cells, metabolism, and immunomodulatory properties of MSCs was analyzed. We...
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Comparison of immunomodulatory properties of mesenchymal stem cells and Sertoli cells
Porubská, Bianka ; Krulová, Magdaléna (advisor) ; Komrsková, Kateřina (referee) ; Filipp, Dominik (referee)
Cell therapies are increasingly considered in preclinical studies and in the future of medicine. The main cell type investigated in this manner is mesenchymal stem cells (MSCs), because of their strong immunomodulatory properties. The efficacy of the therapy depends on various aspects, such as the viability and source of MSCs, the purity of the cell suspension and many more. There is a need for more tailored therapy and the use of cell type better fitting for the specific pathology. Sertoli cells (SCs) are deemed by some authors to be a kind of MSCs, namely because of their similar immunomodulatory properties. Because they reside in the seminiferous tubules in the testes, they are a promising candidate for the treatment of inflammatory pathologies of testicular tissue, such as bacterial infection-induced infertility. In vitro comparison of the ability of MSCs and SCs to differentiate into mesenchymal cell lineages such as osteocyte, chondrocyte, and adipocyte showed success in the case of SCs, providing evidence for their mesenchymal origin. The effect of MSCs or SCs on activated immune cells in vitro showed immunosuppression in both cases with distinct features. MSCs suppressed Th17 cell activation and IL-17 production by CD4+ T cells and SCs down-regulated TNFα and IL-2 production by these cells,...
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Study of differential potential of germ stem cells in vitro in higher vertebrates
Smolík, Ondřej ; Krylov, Vladimír (advisor) ; Krulová, Magdaléna (referee)
Spermatogonial stem cells are unipotent male germ cells which provide spermatogenesis during the whole life. In 2004, an important experiment was conducted. During in vitro cultivation mouse spermatogonial stem cells gained the characteristics of embryonic stem cells, pluripotency by all means. Those cells had the feature to spontaneously differentiate into all three germ layers, endoderm, ectoderm and mesoderm. They also could pass its genetic information to the next generation and they could give rise to teratomas. By this event, experiments started on other vertebrates including rodents, domestic animals and also human. Differentiation of these cells can be directed in vitro to generate specific cell types. On base of these facts, spermatogonial stem cells are alternative source of pluripotent cells which possess many applications in life sciences. The purpose of this thesis is to summarize actual knowledge about differentiation potential in vitro of spermatogonial stem cells in higher vertebrates and try to identify tendencies which they prefer during differentiation, if they exist. Powered by TCPDF (www.tcpdf.org)
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Induction of testicular stem cell differentiation in mammals.
Strnadová, Karolína ; Tlapáková, Tereza (advisor) ; Krulová, Magdaléna (referee)
Stem cells represent a unique cell source with potential usage in regenerative medicine and organ transplantation. As is known, spermatogonial stem cells are unipotent giving rise to a single cell type, which is sperm. Pluripotency was achieved by isolation and cultivation of these testicular stem cells in a number of researches. Testicular pluripotent stem cells differentiated in conditions in vitro to derivatives of all three germ layers identically as embryonic stem cells. The aim of this thesis is to characterize stem cells and summarize the findings of testicular stem cell research. The main focus of this thesis is on studies of cultivated pluripotent stem cells derived from mouse and human testes and their ability to differentiate under determinate conditions into the cells of ectoderm, mesoderm and endoderm.
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Modulation of blood-testis barier by Sertoli cells
Faltýnková, Petra ; Filipp, Dominik (advisor) ; Krulová, Magdaléna (referee)
Sertoli cells in testicles are the main building blocks of the seminiferous tubules where they facilitate the process of spermatogenesis. Although, the Sertoli cells were discovered by Enrico Sertoli more than a 150 years ago, there is still much to discover about their development and functions. The Sertoli cells are critical for the development of germ cells by the provision of hormonal, nutritional and physical support as well as by engulfment of their emerged waste. Since such intimate nurturing interactions with developing spermatocytes require a stable and isolated environment, Sertoli cells themselves create a protected endoluminal compartment sealed off by the blood-testis barrier (BTB). The BTB is a junctional complex formed between adjoining Sertoli cells and serves as an impermeable barrier in the paracellular space. However, spermatogonial stem cell initiating the spermatogenesis lies in front of the BTB closure, hence the developing spermatocytes have to pass through the BTB which is tightly regulated to maintain tissue homeostasis. BTB also exhibits immunological functions, because it can either sequester germ cell-specific antigens from the systemic circulation or release them behind the BTB. The aims of my thesis are to provide a brief overview of Sertoli cell functions in...
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The ion channel TRPV1 and its role in dendritic cells and macrophages
Trnková, Nella ; Krulová, Magdaléna (advisor) ; Vlachová, Viktorie (referee)
This bachelor's thesis deals with the TRPV1 channel and its role in cells of the innate immune system, such as dendritic cells and macrophages. TRPV1 is a membrane ion channel that is activated by physical stimuli such as pH and temperature as well as by substances from the vanilloid group. The most significant of these is capsaicin. Activation of the TRPV1 channel has several effects on different types of cells. Based on the literature review, the bachelor's thesis concludes that the TRPV1 channel tends to lead dendritic cells to have an anti- inflammatory effect. However, there is evidence for both an anti-inflammatory and a pro-inflammatory response in macrophages and the role of TRPV1 is unclear in this cell type. Thus, further research is needed to understand the exact mechanisms of modulation of immune responses and to clarify the role of the TRPV1 channel. Key words: ion channels, TRPV1, capsaicin, dendritic cells, macrophages
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Inhibitory NK cell receptors and possibilities of manipulation of cytotoxic properties.
Švubová, Veronika ; Frič, Jan (advisor) ; Krulová, Magdaléna (referee)
Acute myeloid leukemia makes up for 18 % of all leukemias among pediatric and young adult patients. The complete remission rate (80-90 %) and the overall survival (70 %) of the patients is relatively high, nevertheless, the relapse rate is still almost at 50 % and the prognosis remains extremely bad. The relapse treatment is rather challenging because the persisting leukemic clones might in fact start to be refractory to chemotherapy. Lately, NK cells are being perceived as an attractive therapeutical tool for treatment of the relapses. NK cells are a subpopulation of innate lymphoid cells, possessing the ability to eliminate dysfunctional cells through cytotoxic activities and further perpetuate the immune response. One of the advantages of NK cells is their functional independency of specific antigens. In the light of growing evidence about the role of leukemic stem cells in context of acute myeloid leukemia, NK cells seem to offer a new perspective in therapeutical efforts to eliminate them via several cytotoxic mechanisms. Yet despite optimistic preliminary results, treating this disease has proved to be rather challenging and the NK cell-based immunotherapy is still facing several limitations. Transforming growth factor β is partially responsible for maintenance of leukemic stem cell...
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The Role of TRPV1 in Macrophage Activation and Polarisation
Fikarová, Natálie ; Krulová, Magdaléna (advisor) ; Frič, Jan (referee)
The ability to sense painful stimuli is essential to protect the body. Up to date, the underlying molecular mechanisms are still not completely understood; therefore, the treatment of chronic inflammatory pain remains challenging. The TRPV1 channel is one of the known nociceptors mediating the sensation of burning stimuli. Its agonist is capsaicin, the pungent compound of chilli peppers. This channel has been extensively studied in neurones; however, its function in immune cells is not well understood. Especially in macrophages, data regarding the role of TRPV1 in macrophage polarisation are often contradictory. Thus, further research in this area is desired to clarify the function of TRPV1 in immune cells. This diploma thesis aims to investigate the role of TRPV1 in macrophage polarisation during the inflammatory response. In this work, macrophages were stimulated with capsaicin prior to, after or concurrently with the application of LPS to determine the effect of TRPV1 activation on the inflammatory response. The involvement of MAP kinases in signalling after TRPV1 activation by capsaicin was addressed confirming that ERK 1/2 is part of the signalling cascade. Furthermore, this work proposes that activation of TRPV1 in the context of the LPS-induced inflammatory response could lead to the switch...
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