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Tolerogenic dendritic cells as immune interventions in prevention or therapy of type 1 diabetes
Petrovčíková, Diana ; Funda, David (advisor) ; Hrdý, Jiří (referee)
The main aim of this work is to refer a recent summary of the opportunities and pitfalls of the application of tolerogenic dendritic cells in the prevention or therapy of type 1 diabetes (T1D). Tolerogenic dendritic cells (TolDCs) represent a potential tool for the treatment of allergies, transplant rejections and autoimmune diseases, including T1D, due to their capability to specifically inhibit autoimmune reactions without causing general immunosuppression. TolDCs represent a specific group of dendritic cells and are essential in establishing central and peripheral tolerance. This work presents a helpful guide to better understanding the physiology of tolerogenic DCs and an overview of in vitro generation attempts. In addition, the route of application and migration to target organs has been described. Type 1 diabetes (T1D) is a chronic disease resulting from immune-mediated destruction of the insulin-producing beta cells in the pancreas. Animal models have been invaluable in testing innovative medical treatments since the early testing of insulin in dogs almost a century ago. Animal models of type 1 diabetes (T1D) enable the study of the mechanisms underlying its pathogenesis and the potential development of therapeutic interventions. However, there are still significant gaps in our general...
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Modern therapy of chondral defects
Neckař, Pavel ; Havlas, Vojtěch (advisor) ; Zeman, Petr (referee) ; Tuček, Michal (referee)
The thesis describes the application of cultured bone marrow stem cells in the therapy of focal chondral defect of the knee joint. In the experimental part of the work, the goal was to quantitatively and qualitatively compare two sampling sites of bone marrow monocytic aspirates, the iliac crest bone and the proximal tibia, in order to determine a suitable cell source for advanced cell therapy. The sample analysis showed that the amount of monocytic cells and the yield of stem cells from the aspirate obtained were significantly higher in the bone marrow from the iliac crest. We did not find significant qualitative differences between the two sources of stem cells. In the clinical part of the work, I present a description of the surgical procedure and the results of a 1-year follow-up of patients after the implantation of cultured stem cells from the bone marrow, under the name BiCure® orthoMSCp (Bioinova, Prague, Czech Republic), fixed on a commercially available 3D scaffold Chondrotissue® (BioTissue AG, Geneva, Switzerland) using coagulated autologous platelet-rich plasma. The primary objective of the clinical study included the evaluation of the short-term and long-term safety of the applied medical product. The secondary objective of the work included the assessment of the effectiveness of the...
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Mesenchymal stem cells for treatment of spinal cord injury
Dubišová, Jana ; Kubinová, Šárka (advisor) ; Hock, Miroslav (referee)
Poranenie miechy a jeho terapia pomocou mezenchymálnych kmeňových buniek Abstract Patients with serious spinal cord injury (SCI) have a little chance of a full return to their original life. This kind of injuries leaves lifelong consequences as on the patients themselves, as well as their surroundings and family. Considerable financial resources are, worldwide, granted for reintegratation of these patients into society. This work focuses on the description of spinal cord injury, its complexity and the possibility of treatment by new therapeutic methods of mesenchymal cells. The first section discusses the severity of spinal cord injury and its pathophysiology with the performance of subsequent clinical phases. The second part is dedicated to new treatment methods and approaches, with an emphasis on cell therapy. The third part presents treatment method using mesenchymal stem cells (MSCs), which immunomodulatory and anti-inflammatory properties, such as their ability to migration to the injured area and the possibility of genetic modification, made them a great candidates for the treatment of serious injuries. Keywords Spinal cord injury, stem cells, mesenchymal stem cells, cell therapy, regenerative medicine
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Ethic Consequences of Embryonic Stem Cells Research
Rožánková, Vladimíra ; Ehler, Edvard (advisor) ; Přívratský, Vladimír (referee)
TITLE: Ethic Consequences of Embryonic Stem Cells Research Abstract The thesis deals with stem cell research, especially embryonic cells. First the thesis is devoted to researchand describe the history of stem cells, which focused on embryonicstem cells, which are the central theme of this thesis. This section is also accompanied by visual documentation, for better orientation in the field. The thesis also deals with the issue of stem cell research legislation, focusing in detail on the Czech Republic and Europe. The solution is also the issue of ethical and religious impactofn stem cell research. Key words: law, ethics, embyonic research, cell biology
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Potential of stem cell therapy for diabetic retinopathy
Palacká, Kateřina ; Holáň, Vladimír (advisor) ; Tlapáková, Tereza (referee)
Diabetic retinopathy is retinal disease causing irreversible cell damage and consequently a loss of vision. Current treatment protocols have many limitations and are associated with serious site effects. A possible treatment options for retinal degenerative diseases is a use of stem cells. There are different types of stem cells. These include embryonal stem cells, induced pluripotent stem cells and cells from an adult organism, among which we can include mesenchymal stem cells (MSCs). MSCs can be found in almost all tissues of the adult organism. MSCs can migrate to the site of damage, regulate development of inflammation in retina, suppress the formation of fibrovascular scars and replace damaged cells such as nerve cells, photoreceptors and epithelial pigment cells. Application of MSCs could be a promising treatment for degenerative retinal diseases.
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Generation and application of induced pluripotent stem cells in hematology
Berková, Linda ; Láníková, Lucie (advisor) ; Krulová, Magdaléna (referee)
Induced pluripotent stem cells (iPSC) are one of the key discoveries in cell biology of the last decade. These cells are pluripotent stem cells derived from differentiated somatic cells while having used only four exogenous transcription factors. Pluripotent cells, which can be derived from somatic cells carrying genetic mutation, have a great potential to be used in the testing of new drugs and in discovering molecular mechanisms of genetic disorders. iPSC derived from healthy cells can be used in regenerative medicine. Originally, retroviral vectors were used for delivering reprogramming transcription factors to cells. However such approach is not safe for medicinal use, because of the ability of retroviruses to integrate into the host genome. This fact initiated development of safer delivering methods of transcription factors into the cells. In this work I present the overview of methods which have been used for reprogramming including the most common techniques used to test pluripotency. In addition, I will describe iPSC application options for therapy of genetically determined hematological disorders (sickle cell anemia, β-thalassemia, X-linked chronic granulomatous disease) and for modelling of their molecular mechanism (polycythemia vera). Key words: iPSC, reprogramming, hematological...
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Tolerogenic dendritic cells as a novel cell-based therapy in type 1 diabetes
Kroulíková, Zuzana ; Funda, David (advisor) ; Smrž, Daniel (referee)
Utilization of tolerogenic dendritic cells (tolDCs) as a cell-based therapy represents a promising strategy in treatment of autoimmune diseases including type 1 diabetes (T1D). Numerous protocols have been established to generate tolDCs ex vivo and their therapeutic effect has been demonstrated in animal models of autoimmune diseases. In this thesis we compared three different variants of such protocols which are based on the combined treatment of bone marrow- derived DCs with vitamin D and dexamethasone applied at different time points of their maturation towards tolDCs. We assessed the efficiency of these protocols in regards of their effect on the expression of co-stimulatory molecules CD40, CD80, CD86, and MHC II and the chemokine receptor CCR7 on the surface of tolDCs. Then, we evaluated the migration pattern of antigen unloaded tolDCs in vivo as well as their effect on the induction of immune responses and cell proliferation of lymph node cells. This was achieved by labelling of tolDCs with membrane dye PKH26 and by following their migration path by flow cytometry after intraperitoneal (i.p) or subcutaneous (s.c.) injection into either left or right side of the body. On day 1, 3, 5, 7, and 9, the presence of PKH26+ tolDCs was examined in spleen, pancreatic, mesenteric, inguinal and axillary...
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Potential of stem cell therapy for diabetic retinopathy
Palacká, Kateřina ; Holáň, Vladimír (advisor) ; Tlapáková, Tereza (referee)
Diabetic retinopathy is retinal disease causing irreversible cell damage and consequently a loss of vision. Current treatment protocols have many limitations and are associated with serious site effects. A possible treatment options for retinal degenerative diseases is a use of stem cells. There are different types of stem cells. These include embryonal stem cells, induced pluripotent stem cells and cells from an adult organism, among which we can include mesenchymal stem cells (MSCs). MSCs can be found in almost all tissues of the adult organism. MSCs can migrate to the site of damage, regulate development of inflammation in retina, suppress the formation of fibrovascular scars and replace damaged cells such as nerve cells, photoreceptors and epithelial pigment cells. Application of MSCs could be a promising treatment for degenerative retinal diseases.
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Generation and application of induced pluripotent stem cells in hematology
Berková, Linda ; Láníková, Lucie (advisor) ; Krulová, Magdaléna (referee)
Induced pluripotent stem cells (iPSC) are one of the key discoveries in cell biology of the last decade. These cells are pluripotent stem cells derived from differentiated somatic cells while having used only four exogenous transcription factors. Pluripotent cells, which can be derived from somatic cells carrying genetic mutation, have a great potential to be used in the testing of new drugs and in discovering molecular mechanisms of genetic disorders. iPSC derived from healthy cells can be used in regenerative medicine. Originally, retroviral vectors were used for delivering reprogramming transcription factors to cells. However such approach is not safe for medicinal use, because of the ability of retroviruses to integrate into the host genome. This fact initiated development of safer delivering methods of transcription factors into the cells. In this work I present the overview of methods which have been used for reprogramming including the most common techniques used to test pluripotency. In addition, I will describe iPSC application options for therapy of genetically determined hematological disorders (sickle cell anemia, β-thalassemia, X-linked chronic granulomatous disease) and for modelling of their molecular mechanism (polycythemia vera). Key words: iPSC, reprogramming, hematological...
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