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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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The therapeutic potential of mesenchymal stem cells in a mouse experimental model
Hájková, Michaela
Due to their immunomodulatory and regenerative potential, mesenchymal stem cells (MSCs) represent a promising therapeutic tool for cell-based therapy, organ transplantation or tissue engineering. To improve clinical applicability of MSCs, new methods to increase their delivery and efficacy have been tested in the latest years but the mechanism of observed alterations has not yet been described. In the present project we focused on studying the effect of several factors that can significantly affect the therapeutic success of MSC-based treatment. Initially, we analysed the therapeutic effect of MSCs applied locally on nanofiber scaffold with incorporated cyclosporine A (CsA) in a mouse model of allogeneic skin transplantation. Our results indicate that application of MSCs in the presence of CsA direct M1/M2 macrophage polarization towards regulatory phenotype. This phenotype switching is accompanied by decreased production of nitric oxide (NO) and interferon (IFN-) and increase production of interleukin 10 (IL-10), and may result in suppression of the local inflammatory reaction. The next goal of proposed study was to analyse the effect of the treatment based on MSCs combined with immunosuppressive drugs with different mechanism of action on the balance among distinct T cell subpopulations. We...
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The therapeutic potential of mesenchymal stem cells in a mouse experimental model
Hájková, Michaela ; Krulová, Magdaléna (advisor) ; Hrdý, Jiří (referee) ; Šírová, Milada (referee)
Due to their immunomodulatory and regenerative potential, mesenchymal stem cells (MSCs) represent a promising therapeutic tool for cell-based therapy, organ transplantation or tissue engineering. To improve clinical applicability of MSCs, new methods to increase their delivery and efficacy have been tested in the latest years but the mechanism of observed alterations has not yet been described. In the present project we focused on studying the effect of several factors that can significantly affect the therapeutic success of MSC-based treatment. Initially, we analysed the therapeutic effect of MSCs applied locally on nanofiber scaffold with incorporated cyclosporine A (CsA) in a mouse model of allogeneic skin transplantation. Our results indicate that application of MSCs in the presence of CsA direct M1/M2 macrophage polarization towards regulatory phenotype. This phenotype switching is accompanied by decreased production of nitric oxide (NO) and interferon (IFN-) and increase production of interleukin 10 (IL-10), and may result in suppression of the local inflammatory reaction. The next goal of proposed study was to analyse the effect of the treatment based on MSCs combined with immunosuppressive drugs with different mechanism of action on the balance among distinct T cell subpopulations. We...
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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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Multipotent mesenchymal stromal cells in orthopedic: Potentiation of bone healing
Stehlík, David ; Trč, Tomáš (advisor) ; Janíček, Pavel (referee) ; Sedmera, David (referee)
The aim of the thesis was development of an innovative treatment of bone defects. Human multipotent mesenchymal stromal cells (MSC) play a crucial role in bone healing. Clinical applications of MSC require large amount of cells, which could be obtained by autologous expansion of MSC harvested from bone marrow. As a first step, the standard protocol of MSC expansion based on αMEM medium and fetal bovine serum (FBS) was used. Experiments replacing FBS by pooled human serum (HS) in the culture medium concluded in patenting of a new MSC cultivation protocol (EU 1999250, CR 301141). This one-step cultivation protocol and xenogeneic protein-free cultivation medium is based on CellGro® for Hematopoietic Cells' Medium, HS, human recombinant growth factors, dexamethasone, insulin and ascorbic acid. The preclinical in vitro and in vivo experiments with MSC from both expansion protocols were carried out. Fibrillar polylactic scaffolds were seeded with MSC, cultured, differentiated and implanted in immunodeficient mice (NOD/LtSz-Rag1-). Bone-like mineralized tissue containing vessels was observed. The MSC cultured according to patented method were classified as Advanced-therapy Medicinal Product and has to fulfil the European Medicines Agency regulations to enter the clinical trials. Nevertheless the use of MSC seems...
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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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Local and systemic pathological processes in diabetic foot diasease and their management
Dubský, Michal ; Jirkovská, Alexandra (advisor) ; Rušavý, Zdeněk (referee) ; Karetová, Debora (referee)
Local tissue factors, ischemia and infection (which are often the cause of re-ulceration) are the main pathogenetic factors for diabetic foot disease (DFD). Neuropathic bone metabolism disorder leads to Charcot osteoarthropathy (CHOA). The aim of this dissertation was to assess experimentally the effectiveness of new skin substitutes, evaluate local vasculogenesis in different types of cell therapy of DFD, the role of infection in recurrence of DFD and scintigraphic parameters of activity of CHOA. Our studies concerning local pathological processes in DFD experimentally proved that gelatine nanofibers accelerate wound healing and can be suitable scaffolds for cell transfer and skin regeneration and also that acellular porcine dermis is more effective in healing of chronic wounds then xenotransplants. Our studies concerning therapeutic vasculogenesis confirmed that efficacy of stem cells (SC) harvested from bone marrow is similar in efficacy to SC separated from peripheral blood after stimulation. We found no evidence for systemic vasculogenesis by means of a significant increase of pro-angiogenic cytokines, which confirms the paracrine effect of injected SC. We proved a significant correlation between angiogeneisis inhibitor (endostatin) and the number of injected SC, which could be an indicator of...
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Targeted differentiation of mesenchymal stem cells and their clinical application
Hámor, Peter ; Kubinová, Šárka (advisor) ; Trošan, Peter (referee)
The goal of this work is to point out possibilities of neuronal differentiation of mesenchymal stem cells and their application for clinical purposes, primary for repairing and regeneration of central nervous system tissues. Because this system works as a control center for functional features of the whole body, and treating this injuries and degenerations often bring many problems and obstacles, the possibility of using autologous cells for a transplantation or inducer of the natural regenerative properties of tissues is worth deeper research. This work progressively focuses on basic characteristics of stem cells and their differentiation potential, characterizing further mesenchymal stem cells together with possibilities of their isolation and cultivation. The main part of the text is formed by studies and methods used for targeted differentiation of mesenchymal stem cells and attempts of their transdifferentiation into neural cell line, together with present and possible future application of these cells in central nervous system therapies.
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Cell therapy in animal models - preclinical studies
Juhásová, Jana ; Motlík, Jan (advisor) ; Grim, Miloš (referee) ; Jendelová, Pavla (referee)
The progress of cell therapy can be greatly facilitated by using suitable experimental models. It is essential to verify the clinical usefulness of new healing procedures obtained in studies on laboratory animals by using a large animal model. One of suitable models well acceptable in medical community is undoubtedly the miniature pig, which resembles humans in terms of physiology and body proportions. This PhD thesis presents the summary of our experimental studies relating to possible exploitation of mesenchymal and neural stem cells in the healing of locomotive apparatus and neural tissue disorders in humans or animals. The first part of the thesis briefly describes the current issue of cell therapy and animal models, mesenchymal cells and/or their combination with new types of scaffolds, neurogenesis, neural stem cells and their potential application in therapy of spinal cord injury. The second part is focused on the goals and methodology, the individual publications being listed in the third part. Our experiments with iatrogenic physeal defect in rabbits, which served as a model of the occurrence of valgous deformation in the clinical practice, showed the positive preventive and therapeutical effects of a new type of scaffolds seeded with allogeneic mesenchymal stem cells in animals without...
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