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The role of stem and progenitor cells in regeneration of hematopoietic tissue
Faltusová, Kateřina ; Nečas, Emanuel (advisor) ; Hofer, Michal (referee) ; Filipp, Dominik (referee)
Tissue regeneration is a complex and highly orchestrated process dependent on cells with the potential to restore structures and functions and on controlling factors from the tissue microenvironment. Hematopoietic tissue has a high ability to regenerate, which is attributed to the presence of stem cells, but the regeneration of severely damaged adult tissue is still only partially understood. Hematopoietic tissue provides a unique opportunity to study tissue regeneration due to its well-established steady- state structure and function, easy accessibility, advanced research methods, and well-defined embryonic, fetal, and adult stages of development. Embryonic/fetal liver hematopoiesis and adult hematopoiesis recovering from damage share the needto expand populations of progenitors and stem cells in parallel with increasing production of mature blood cells. We analyzed adult hematopoiesis in mice subjected to a submyeloablative dose (6 Gy) of gamma radiation, in which only a few cells with reconstituting capacity survived. We targeted the period of regeneration characterized by the renewed massive production of mature blood cells and the ongoing expansion of immature hematopoietic cells. Cells from the top of the hematopoietic hierarchy, hematopoietic stem cells, and multipotent progenitors are almost missing...
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Bioindikátory zánětu, oxidačního a nitračního stresu u potkana kmene Wistar po celotělovém a lokálním ozáření plic
Nagy, Andrea ; Chládek, Jaroslav (advisor) ; Hofer, Michal (referee) ; Štětina, Rudolf (referee)
6 3 SUMMARY Bioindicators of inflammation, oxidative and nitrossative stress in Wistar rats after whole-body and lung irradiation Introduction Radiation pneumonitis and fibrosis limitthe intensity of radiotherapy,increase morbidity and worsen quality of life of patients with lung and breast cancer or Hodgkin's disease. Radiation pneumonitis is an acute inflammatory reaction that resolves either spontaneously or after treatment with corticosteroids. Free radicals play an important role in its etiology. They cause dose-dependent induction of lipoperoxidation, DNA damage, activation of proapoptotic events and changes in activity of enzymes. The inflammatory reaction initiated by free radicals affects primarily epithelial and inflammatory cells, which release a number of cytokines (TNF-α, IL-1, IL-6, TGF-β, etc.). Radiation fibrosis of lungdevelops as a late consequence of radiotherapy (> 3 months). It can lead to chronic respiratory failureand death. Macroscopic findingsincludefibroblastproliferation,collagen deposition and destruction of lung parenchyma. Aims and methodology This work was focused on the changes in the arginine-nitric oxide metabolic pathway induced in the airways, lung and other parts of the body by ionizing gamma radiation in the early phase (within 72 h) as well as in the phase of radiation...
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Transplantace kostní dřeně příjemcům s regenerující krvetvorbou: účinnost transplantace a stav regenerující kostní dřeně
Forgáčová, Katarína ; Nečas, Emanuel (advisor) ; Vávrová, Jiřina (referee) ; Hofer, Michal (referee)
Hematopoietic stem cells (HSCs) have the ability of both self-renewal and differentiation. After bone marrow damage, surviving host HSCs or transplanted donor HSCs are able to restore hematopoiesis and maintain it for a long time due to the self-renewal potential. HSCs reside in a specific microenvironment in the bone marrow, in stem cell niche, which supports their survival and controls their functioning. In this study, we investigated the impact of bone marrow damage induced by increasing doses of irradiation on engraftment efficiency of transplanted donor repopulating cells. Using the CD45.1/CD45.2 congenic mouse model, we developed a new approach enabling estimation of surviving HSCs in damaged hematopoietic tissue. Its principle is in measuring of the donor chimerism resulting from transplantation of a defined dose of normal congenic bone marrow cells. The transplanted donor cells contain repopulating cells, progenitors (STRCs) and HSCs (LTRCs) that give rise to blood cell production which proceeds in parallel with that present in the host hematopoietic tissue. We applied this approach to monitor spontaneous regeneration of repopulating cells, including HSCs, in mice irradiated with a sublethal dose of 6 Gy or by a lethal dose of 9 Gy and rescued by syngenic bone marrow cells. This was...
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Changes in protein expression in response to genotoxic stress
Ćmielová, Jana ; Řezáčová, Martina (advisor) ; Hofer, Michal (referee) ; Šinkorová, Zuzana (referee)
Human mesenchymal stem cells from the bone marrow, the dental pulp and the periondontal ligament are known for their high proliferation potential and the ability of self-renewal comparable to the other stem cells. They represent a promising field in the therapy due to their ability to differentiate into many cell types. On the other hand, these cells persist in the organism for a long time and a damage in their genetic material would result in mutation of cell genome. The characterization of these cells under genotoxic stress is therefore important. Ionizing radiation is one of the powerful DNA-damaging stressors causing cell cycle arrest associated with reparation or apoptosis. The aim of our work is to study the effect of ionizing radiation on mesenchymal stem cells from the bone marrow, the dental pulp and the periondontal ligament and the response of these cells to ionizing radiation after ATM kinase inhibition. ATM kinase is thought to be a key molecule reflecting DNA damage, especially double strand breaks. We evaluated molecular mechanisms of the apoptosis induction and the reaction to DNA damage caused by ionizing radiation in mesenchymal stem cells isolated from bone marrow, dental pulp and periodontal ligament. The main result of our work is that after the irradiation these cells do not...
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Primary Cilia and its Importance in Cell Response to Ionizing Radiation Exposure and Chemotherapy Drugs.
Filipová, Alžběta ; Řezáčová, Martina (advisor) ; Hampl, Aleš (referee) ; Hofer, Michal (referee)
Primary cilia and its importance in cell response to ionizing radiation exposure and chemotherapy drugs. Ionizing radiation, metabolic and genotoxic stress affect the cytoskeletal stability and morphology of cells by causing DNA damage in the form of single or double stranded breaks, the latter being the most critical. When DNA damage occurs the cell cycle becomes arrested and the repair machinery is engaged; however, if this damage is not repaired the cell enters programmed cell death by apoptosis. Primary cilia have been shown to act as physical- chemical sensors and their biological functions include the perception of the extracellular milieu, the regulation of organogenesis and cell polarity, as such, they are dynamically regulated during cell cycle progression. Further, the impairment or loss of primary cilia leads to the development of ciliopathies and other diseases including cardiovascular disorders, arthritis and, ultimately, cancer. Moreover, the presence and temporary formation of primary cilia is essential for the repair process of certain cell types. This work is focused on the evaluation of primary cilia changes caused by ionizing radiation, metabolic stress or cytostatic drugs (taxol and doxorubicin) in vitro. Our results showed a significantly higher number of ciliated C2C12 cells observed...
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