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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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Gamma-delta T lymphocytes in adipose tissue
Sztoláriková, Adéla ; Krulová, Magdaléna (advisor) ; Pačes, Jan (referee)
T lymphocytes are a unique type of T lymphocytes which, because of their innate-like qualities, belong to the so-called innate lymphocytes. Although they are a relatively rare population of T lymphocytes in peripheral blood, they are enriched in many peripheral tissues where they participate in immune responses to infectious pathogens and cell transformation. In addition, they play a role in the development of several autoimmune disorders. Recently, non- immune functions of T lymphocytes in tissue repair and tissue homeostasis have also been emphasized. This work focuses on the characterization of T lymphocytes, especially those residing in adipose tissue. T lymphocytes regulate adipose tissue homeostasis and overall energy metabolism. The roles of T lymphocytes under physiological and non-physiological conditions are described, including their impact on the development of obesity and metabolic syndrome. The possible applications of these lymphocytes in the treatment of these diseases are also briefly mentioned.
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Mitochondrial transfer and its role in regenerative properties of mesenchymal stem cells
Jaborová, Natálie ; Krulová, Magdaléna (advisor) ; Nahácka, Zuzana (referee)
Mitochondrial transfer represents a form of intercellular communication. In this process, mitochondria are delivered from the donor cell to the recipient cell through several structures. The transfer of mitochondria is observed under pathological and physiological conditions and is accompanied by specific signaling. Mitochondria uptake by injured cells promotes tissue regeneration. This bachelor thesis discusses general knowledge of mitochondrial transfer focusing on mesenchymal stem cells (MSCs) as a donor cell type. Furthermore, the regenerative effect of MSC-derived mitochondria transfer to cells damaged by various pathologies is summarized. In this regard, MSCs have significant therapeutic potential that could be used in future clinical strategies for a number of diseases. Keywords: mitochondria, transfer, mesenchymal stem cells, regeneration
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