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Immunomodulatory properties of mesenchymal stem cells from patients with amyotrophic lateral sclerosis and healthy donors
Matějčková, Nicole
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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Clinical applications of stem cells for the treatment of neurodegenerative diseases of CNS
Jančová, Pavlína ; Kubinová, Šárka (advisor) ; Heřmánková, Barbora (referee)
Stem cells have a huge therapeutic potential due to their ability to differentiate in multiple tissues. They could be used for neurodegenerative diseases treatment, which are typical for loss of specific groups of neurons, progressive course and lack of effective treatment due to their complicated pathophysiology, only therapies for elongation and simplification of patients' life are available. This thesis summarizes results of completed clinical studies and informs about ongoing studies, in which stem cell treatments are used for selected neurodegenerative diseases. Stem cell therapy for multiple sclerosis and amyotrophic lateral sclerosis have a long history, some of the studies has proven therapeutic efficiency of stem cells. We don't know much about effect of stem cell treatment for patients with Alzheimer's and Parkinson's diseases, because first clinical studies were finished recently. But all clinical trials have proven safety of stem cell treatment. Replacement of damaged neurons haven't been reached yet, just protection of remaining neurons by neurotrophic and immunomodulatory factors secreted by stem cells. Keywords: neurodegenerative diseases, stem cells, clinical trials, multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease
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Influence of parcellation atlas on quality of classification in patients with neurodegenerative dissease
Montilla, Michaela ; Lamoš, Martin (referee) ; Gajdoš, Martin (advisor)
The aim of the thesis is to define the dependency of the classification of patients affected by neurodegenerative diseases on the choice of the parcellation atlas. Part of this thesis is the application of the functional connectivity analysis and the calculation of graph metrics according to the method published by Olaf Sporns and Mikail Rubinov [1] on fMRI data measured at CEITEC MU. The application is preceded by the theoretical research of parcellation atlases for brain segmentation from fMRI frames and the research of mathematical methods for classification as well as classifiers of neurodegenerative diseases. The first chapters of the thesis brings a theoretical basis of knowledge from the field of magnetic and functional magnetic resonance imaging. The physical principles of the method, the conditions and the course of acquisition of image data are defined. The third chapter summarizes the graph metrics used in the diploma thesis for analyzing and classifying graphs. The paper presents a brief overview of the brain segmentation methods, with the focuse on the atlas-based segmentation. After a theoretical research of functional connectivity methods and mathematical classification methods, the findings were used for segmentation, calculation of graph metrics and for classification of fMRI images obtained from 96 subjects into the one of two classes using Binary classifications by support vector machines and linear discriminatory analysis. The data classified in this study was measured on patiens with Parkinson’s disease (PD), Alzheimer’s disease (AD), Mild cognitive impairment (MCI), a combination of PD and MCI and subjects belonging to the control group of healthy individuals. For pre-processing and analysis, the MATLAB environment, the SPM12 toolbox and The Brain Connectivity Toolbox were used.
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Vývoj, optimalizace a validace analytické metody na stanovení neurotoxinu beta-N-methylamino-L-alaninu ve vodě a sinicích pomocí LC/MS
HOŘEJŠÍ, Karel
This master thesis deals with the development, optimization and validation of an analytical method for determination of neurotoxin -N-methylamino-L-alanine in pond water and cyanobacteria using LC/MS. Firstly, basic parameters of the analytical method developed within authors´s bachelor thesis were verified. Following parameters were selected for verification: selection of suitable MRM transitions, voltage applied to S-lens and F-lens and standardized collision energy. Secondly, the system suitability testing was performed. Thirdly, the analytical method was successfully validated. Then, the testing and optimization of solid phase extraction for analysis of water samples were carried out. The pH of sample solution and composition of elution solution were chosen for the optimization. In addition, the trichloroacetic acid extraction with acid hydrolysis for cyanobacterial samples was carried out too. Finally, both solid phase extraction and trichloroacetic acid extraction were evaluated and applied to the analysis of real samples.
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Central nervous system plasticity in adulthood and after injury.
Procházková, Natálie ; Jendelová, Pavla (advisor) ; Chmelová, Martina (referee)
Perineural nets are a structure of extracellular matrix, enwrapping several subpopulations of neurons in the central nervous system. Their formation is linked to the closure of critical period and significant plasticity restriction. In a healthy organism, they are important for stabilisation of mature nervous system, support of highly active neurons, and neuroprotection. However, they are one of the factors that restrict tissue regeneration during pathological conditions by participating in the formation of glial scar and upregulating molecules that have inhibitory impact on neuron sprouting. Digestion of perineuronal nets, which is mostly achieved enzymatically, leads to re-opening of critical period and renewal of plasticity, potentiating neuronal sprouting and growth and overall regeneration of central nervous system after mechanical damage, such as spinal cord injury, or during neurodegenerative diseases, as is Alzheimer's disease. Perineural nets play a similar role in Alzheimer's disease and aging, where they participate in memory loss. Renewal of plasticity in these conditions leads to facilitation of synaptic transmission and therefore eliminating the memory deficit. Key words: neurodegenerative diseases, CNS injury, Alzheimer's disease, perineural nets, chondroitinsulfate proteoglycans
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The use of induced pluripotent stem cells in the treatment of spinal cord injury and ALS.
Gajdoš, Roman ; Jendelová, Pavla (advisor) ; Vargová, Lýdia (referee)
Induced pluripotent stem cells (iPSCs) have become a new phenomenon of regenerative medicine. It is obvious that they share some common characteristics with embryonic stem cells (ESCs) such as stemness potential, self-renewal p., differentiation p. iPSCs retain their epigenetic memory, allowing becoming patient-specific and so it is not necessary to apply immunosuppressants. The use of ESCs is controversial, because their acquisition is associated with embryo destruction. As a cell source for iPSCs derivation we can use any somatic cells, however, fibroblasts are preferably used due to their easy availability. With transcriptional reprogramming cocktail (OCT4, SOX2, KLF4, c- MYC / OCT4, SOX2, NANOG, LIN28) we can obtain required iPSCs line, which is then further differentiated into neural precursors (NPCs). These cells can be grafted into lesion site, where they can facilitate regeneration by several mechanisms (cell replacement, protective effect, facilitation the expression of trophic factors). Nevertheless, here we are still dealing with the risk of tumorogenesis or low cell derivation efficiency that limits the use of iPSCs in clinical practice. In this thesis we will therefore mainly focus on the therapeutic potential of iPSCs in preclinical studies, their use in the treatment of...
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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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Changes in neuroglia in degenerative disorders of the central nervous system
Kirdajová, Denisa ; Zach, Petr (advisor) ; Hock, Miroslav (referee)
Neurodegenerative diseases are a serious disorders of the central nervous system characterized by neuronal loss with a subsequent damage of the brain. This damage may have diverse consequences like a gradual loss of memory and intellect, problems with musculoskeletal system and not least death. Causes of these diseases are not yet fully understood. In addition to neurons neuroglia also plays an important role in these diseases of the central nervous system. In neurodegenerative diseases are astrocytes, oligodendrocytes, microglia and NG2 cells involved in their many aspects. They participate in the protective as well as in the detrimental aspect of these diseases. This work, therefore, presents an overview of previously acquired knowledge of neuroglia in various types of degenerative disorders of the CNS (Alzheimer`s disease, Parkinson`s disease, amyotrophic lateral sclerosis, multiple sclerosis, Wernicke encephalopathy, HIV associated dementia, frontotemporal dementia, vascular dementia). Powered by TCPDF (www.tcpdf.org)
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The role of nitric oxide in the patophysiology of neurodegenerative diseases
Matušková, Hana ; Otáhal, Jakub (advisor) ; Alánová, Petra (referee)
The bachelor thesis deals with the importance of nitric oxide in the development of neurodegenerative diseases. Nitric oxide is a biological active gas which affects, among other things, many functions of the central nervous system. Its activity is dependent on the concentration in small amounts has a positive effect, while overproduction contributes significantly to the development of neurodegenerative diseases. In my work, I deal with the negative influence of nitric oxide in the development of epileptic seizures, Parkinson's disease, Alzheimer's disease and Huntington's disease. In conclusion, I mentioned the possibility of determining the amount of nitric oxide concentration. Keywords Nitric oxide, ROS, RNS, neurodegenerative diseases, epileptic seizures, Parkinson's disease, Alzheimer's disease, Huntington's disease
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Vývoj, optimalizace a validace analytické metody na stanovení neurotoxinu \recke{beta}-N-methylamino-L-alaninu ve vodě pomocí LC/MS
HOŘEJŠÍ, Karel
This bachelor thesis deals with the development, optimization and validation of an analytical method for determination of neurotoxin \recke{beta}-N-methylamino-L-alanine in water using LC/MS. At first, the development and optimization of the analytical method was performed. For the optimization of the analytical method following parameters were selected: temperature of HESI and MS capillary, gases flow rate, voltage on S-lens, F-lens and capillary, collision energy. In addition, mobile phase composition, flow rate of mobile phase and injection volume of sample were optimized too. Then, the analytical method was successfully validated. Finally, the method was applied to the analysis of real samples of surface water.
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