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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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Plasma modification of functionalized PVA nanofibers for the enhancement of mesenchymal stem cell adhesion, viability and proliferation.
Bezděková, Dagmar ; Amler, Evžen (advisor) ; Gášková, Dana (referee)
Electrospinning is widely used technique to produce nanoscale constructs for tissue engineering. This technique can be used to spin wide range of polymers. One of them is polyvinyl alcohol (PVA), which has very good properties for use in this field. PVA is nontoxic, has good mechanical strength and it's degradable and biocompatible. Electrospun PVA nanofibers have limitations because of their -OH side groups. These groups cause solubility of PVA in water. The solubility can be adjusted with crosslinking techniques, but PVA still remains very hydrophilic, which is causing low adhesion of cells. In recent research we decided to reduce the hydrophilicity of PVA using plasma modification. Polymer modification with cold plasma is an economic and quite simple process to change the surface chemistry without side effects that come with conventional chemical treatment. With radical, formed by discharge, we have deposited hydrocarbons on the PVA surface and we rapidly increased hydrophobicity of the polymer surface. The change of surface chemistry has only a little effect on the fiber morphology. The increase of hydrophobicity allowed better adhesion of mesenchymal stem cells on plasma modified PVA as compared to non-modified PVA and a huge change in cell morphology was observed. These changes suggest that we...
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Characterization of functionalized fibres for mesenchymal stem cells cultivation and differentiation
Greplová, Jarmila ; Amler, Evžen (advisor) ; Rosina, Jozef (referee)
Modification of nanofibers is an actual trend in tissue engineering. Polyvinylacohol (PVA) is nontoxic and biodegradable polymer suitable for preparation of submicron fibers by electrospinning. Main disadvantage of PVA fibers is rapid degradation in aqueous environment. On the other hand surface of fibers contains free hydroxyl group that could be chemically modified. In recent work, chemical modification of PVA nanofibers prepared by needleless electrospinning was investigated. Polyethylenglykol (PEG) linker was introduced to the fiber surface by acylation (PVA-PEG) and further modified by biotin (PVA-PEG-b) as a function agent. Process of chemical modification does not affected fibrous morphology of samples. Interestingly, linkage of PEG-b linker promoted stability of PVA in aqueous environment. PVA-PEG-b sample was stable for 41 days. Stability of samples was strongly dependent on amount of introduced PEG-b linker, thus proposed method of modification allows to prepare nanofibers of different solubility. Additionally, biocompatibility of chemically modified nanofibers with both mesenchymal stem cells (MSC) and chondrocytes was determined. Proliferation of both cell types was not sufficient and number of cells decreased in time, probably because of high hydrophility of modified PVA scaffold. To...
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Modulation of mesenchymal stem cell properties and their use in the regulation of transplantation immunity
Peřinová, Lucie ; Krulová, Magdaléna (advisor) ; Zajícová, Alena (referee)
Mesenchymal stem cells (MSCs) represent a heterogeneous population of stromal cells with a pluripotent differentiation potential. They can be isolated from multiple tissues of mesodermal origin, such as bone marrow, adipose tissue, umbilical cord blood and peripheral blood and afterwards externally expanded according their adherence to the plastic surfaces. These cells show remarkable immunomodulatory properties, suppressing T-, B- and NK-cell functions, and also modulating dendritic cell activities and influencing immune responses during tissue repair and recovery. MSCs have been shown to possess ability to migrate to sites of inflammation and tissue injury. All these properties make MSCs a promising tool for clinical application. Our primary goal was to identify processes that may influence immunoregulatory effects of MSCs. In order to promote immunossupressive qualities of MSCs we established the scheme comprising MSCs precultivated with various cytokines and Toll-like receptors (TLR) ligands in vitro, with the final aim to improve the therapeutic effect of MSCs on wound healing in vivo. We studied modulation of MSCs properties and consequently the effect of influenced MSCs on cells of the immune system. The immunosuppression is mainly mediated through secreted factors that MSCs produced after...
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Mesenchymal stem cells and the possibility of their transdifferentiation into insulin producing cells.
Dostálová, Veronika ; Holáň, Vladimír (advisor) ; Čečrdlová, Eva (referee)
Mesenchymal stem cells (MSCs) have been demonstrated in almost all tissues of the body. Their main source is bone marrow and adipose tissue. These cells are multipotent, e.g. they are capable of differentiating into a variety of cell types. They are able to migrate into damaged tissues. Their other relevant property is a specific suppression of imunity. In the body they serve as precursors for specialized cell types and they also participate in formation of specific tissue microenvironment. Their properties represent a great potential in a wide range of clinical therapies. Besides other possible applications they could be used in the therapy of diabetes mellitus type one. During this disease insulin producing -cells are destroyed. MSCs have been used in experimental in vitro and in vivo studies to differentiate into insulin producing cells. However these cells are not able to produce sufficient amounts of insulin to exclude the supportive administration of exogenous insulin. Therefore there is a need for further research in this field of possible therapy.
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The influence of Toll-like receptors on immunomodulatory properties of mesenchymal stem cells
Heřmánková, Barbora ; Krulová, Magdaléna (advisor) ; Indrová, Marie (referee)
Immunosuppressive properties of mesenchymal stem cells (MSCs) offer potential tools for cell-based regenerative therapy and immunotherapy. MSCs express a large number of Toll like receptors (TLRs) recognizing multiple pathogen-associated molecular patterns (PAMPs), which could be found in patients microenvironment and modulate activity of MSCs. TLR ligands could lead to modulation of proliferation, differentiation, immunosuppression, migration, polarization and production of cytokine. This work discusses the effect of TLRs on immunomodulatory properties of MSCs, because there are lots of contrasts in the results about their effect.
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Targeted differenciation of limbal and mesenchymal stem cells and their therapeutic application
Kuthanová, Hana ; Holáň, Vladimír (advisor) ; Indrová, Marie (referee)
The research of stem cells slowly transfers from the experimental to the preclinical and clinical level. They are in the centre of interest thanks to their potential to treat many of severe injuries and genetically determined diseases. However, the clinical application of these cells has to be based on a basic research of their characteristics and differential potential. Adult stem cells are in organism in minor populations in unique niches. In comparison with embryonic and induced pluripotent stem cells, the adult stem cells have lower differential potential but they also tend less to making teratomas. The therapeutic use of differential and transdifferential potential of limbal and mesenchymal stem cells is described here in more detail with focus on their use in damaged ocular surface treatment. Limbal stem cells are the only source of stem cells for corneal epithelium regeneration in most organisms. Deficiency of these stem cells leads to severe eye disorders even to blindness. Nowadays, a transplantation of allogeneic limbal stem cells or allogeneic limbus is the only chance for patients with total limbal stem cell deficiency. In clinical trials with patients with particular limbal stem cell deficiency, autologous limbal stem cells were successfully transplanted. Mesenchymal stem cells derived...
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Immunomodulatory properties of mesenchymal stem cells - use in therapy
Pavlíková, Michaela ; Stříž, Ilja (referee) ; Krulová, Magdaléna (advisor)
Mesenchymal stem cells (MSC) are extensively studied mainly due to their feasible clinical application. Therapeutic potential of MSC consists not only of the ability to differentiate into mesenchymal cells, ectodermal and endodermal cell lines, but primarily in their immunomodulatory functions. Due to their effect on immune cells, MSC promote the shift of the inflammatory immune response to antiinflammatory. The ability to suppress inflammation, together with their differentiation potential and antiapoptotic potential on the surrounding cells makes MSC a promising tool for treating serious diseases. This work discusses the effect of MSC on the individual cells of the immune system. It focuses on the description of the effect of MSC in four model cases. These are an experimental autoimmune encephalomyelitis, myocardial infarction, diabetes mellitus and skin graft transplantation. The knowledge of the mechanisms of the interactions between MSC and the cells of the immune system, together with the understanding the effect of specific conditions on MSC is essential for their use in clinical therapy. Keywords: mesenchymal stem cells, immunomodulation, autoimmune diseases, transplantation
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