National Repository of Grey Literature 20 records found  1 - 10next  jump to record: Search took 0.00 seconds. 
Anti-inflammatory compounds and stem cells in treatment of spinal cord injury
Kárová, Kristýna ; Jendelová, Pavla (advisor) ; Sameš, Martin (referee) ; Chvátal, Alexandr (referee)
Despite intense scientific efforts, spinal cord injury (SCI) remains to be a severe neurological condition that has no treatment. Currently, therapy is based on alleviating pressure by surgical spinal cord decompression, administration of methylprednisolone and physical therapy. In this study, therapeutic effects of anti-inflammatory compounds and of three types of stem cells were tested in a balloon compression model of spinal cord injury in rats. Natural compounds epigallocatechin-3-gallate (EGCG) or curcumin were administered in situ and then intraperitoneally every day for up to 28 days. Human bone marrow mesenchymal stem cells (MSCs), human spinal neural precursors (SPC-01) and neural precursors derived from human induced pluripotent stem cells (iPS-NPs) were transplanted intrathecally (MSCs) or via spinal injection into immunosuppressed rats 7 days after induction of SCI. To determine effects of therapies, changes in motor function was tested by open field test BBB, flat beam test and score, Plantar test and rotarod. Morphometric analysis was used to assess gray/matter sparing and cavity size. Immunohistochemistry was used to determine survival and differentiation of transplanted cells, activation of classical pathway of NFκB (p65 nuclear translocation), astroglial activation (GFAP) and...
Cellular Reprogramming as a Tool for Harvesting Patient-specific Stem Cells
Pisal, Rishikaysh ; Mokrý, Jaroslav (advisor) ; Hampl, Aleš (referee) ; Jendelová, Pavla (referee)
Cellular reprogramming as a tool for harvesting patient specific stem cells In the year 2006, Dr. Yamanaka surprised the entire field of medicine, by reporting a technique of inducing pluripotency in somatic cells. In his article, he had displayed that fibroblasts could be reprogrammed to pluripotent stem cell state, by ectopic expression of four transcription factors namely OCT4, SOX2, c-MYC and KLF4. His discovery made a paradigm shift in the field of reprogramming because previous methods of reprogramming were dependent on use of human oocytes and this raised ethical concerns. Moreover, his technique of cellular reprograming broadened the spectrum of application of somatic cells in regenerative medicine. Objectives of my research were focused on; development of an optimised protocol for detection of mycoplasma that commonly infects animal tissue culture; detailed characterization of reprogrammed clones; targeted differentiation of iPSC towards myogenic lineage, and construction of an expression vector, optimised for miRNA expression. For detecting mycoplasma infection, we adapted the protocol of Uphoff et al. (2002). By skipping the DNA extraction step (reported in the original protocol) and instead directly using cell culture supernatant and a robust polymerase enzyme for performing PCR, we...
Studium interakce buněk s biomimetickým materiálem a jeho využití v biomedicíně
Sauerová, Pavla ; Hubálek Kalbáčová, Marie (advisor) ; Vandrovcová, Marta (referee) ; Jendelová, Pavla (referee)
Biomaterials are considered as very promising tools for regenerative medicine. They have compensatory or supporting function in organism and they are often developed to support specific conventional medical procedures. So-called biomimetic materials are developed to imitate natural environment of organism and to induce positive innate responses of organism. An essential part of biomaterial development is in vitro biological evaluation, which characterizes (often for the first time) the potential of developed material for its clinical application. This Ph.D. thesis deals with in vitro biological evaluation of three different biomimetic materials. In all three cases, the comprehensive evaluation was an integral part of the material development and optimization processes. Each material was in vitro characterised at the level of cell-material interactions with respect to its intended specific application.. In the first part, cell response to potential drug delivery system based on colloidal complexes of cationic surfactants with hyaluronic acid (HyA) was characterized. HyA protection ability and its limits were described; also the role of fetal bovine serum (FBS) in cell response to the stress stimuli was confirmed. Results considered surfactant-HyA complexes as promising system for drug delivery. In...
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
The role of link proteins in the stabilization of the brain extracellular matrix and in formation and maintaining of the perineuronal nets
Suchá, Petra ; Vargová, Lýdia (advisor) ; Jendelová, Pavla (referee)
The brain extracellular space (ECS) contains specified macromolecules forming the extracellular matrix (ECM), containing a high amount of negative charges that could bind water or other soluble ions and molecules diffusing within the ECS. In specific brain areas, the ECM molecules form a condensed, reticular-like structure of perineuronal nets (PNNs). It has been found that PNNs appear at the end of the critical period, when they stabilize the synapses and terminate their plasticity and may have also neuroprotective function. To study the role of brain link protein 2 (Bral2) in stabilizing the ECM complexes, we employed the real-time iontophoretic method and immunohistochemical analysis to show the difference in the ECS diffusion parameters and level of expression of the ECM molecules between the wild type and Bral2-deficient mice. We also compared changes in the ECS diffusion parameters induced by Bral2 deficiency with those appeared after enzymatic destruction of the ECM by the chondroitinase ABC (chABC). In the Bral2-deficient mice, we discovered significantly decreased values of tortuosity in the trapezoid body. This difference was age related and did not manifest itself in young mice. Immunohistochemical analysis showed that inferior colliculus does not contain Bral2-brevican based...
The biocompatibility and potential cytotoxicity of materials for joint replacement manufacturing and coating
Kopová, Ivana ; Bačáková, Lucie (advisor) ; Hubálek Kalbáčová, Marie (referee) ; Jendelová, Pavla (referee)
Currently used prostheses for total joint replacement still have numerous disadvantages: extreme stiffness or elastic modulus of the bulk metallic material; insufficient integration of the implant into the host bone; and a high wear and corrosion rate, which causes an accumulation of mostly metallic or polymeric wear debris. Because of these reasons, many patients experience increasing local pain, swelling, allergic reactions, and inflammation resulting in bone loss and the aseptic loosening of the implant leading to the need for painful and expensive revision surgery. To address the mechanical issues of commonly used orthopaedic alloys, this thesis presents the development of the new β-type titanium alloy Ti-35Nb-7Zr-6Ta-2Fe-0.5Si with a relatively low elastic modulus (up to 85 GPa), increased tensile strength (880 MPa), and enhanced biocompatibility and osteoconductivity. Considering the generally low osteoinductivity of metallic implants, various surface modifications and coatings have been developed to improve the cell-material interaction, e.g. carbon-based coatings. Among these coatings, C60 fullerene layers have emerged as a great candidate for coating orthopaedic implants due to their therapeutic potential in arthritis. The potential cytotoxicity and DNA damage response of fullerenes have...
The use of stem cells in the experimental model of stroke
Turnovcová, Karolína ; Jendelová, Pavla (advisor) ; Bojar, Martin (referee) ; Mazurová, Yvona (referee)
Human stem cells from diverse origin are a most promising source for innovative therapy in acute brain lesions. Here, we evaluated the potential of human pluripotent cell-derived neural precursor therapy in stroke, we studied growth properties and surface marker expression of human mesenchymal stromal cells cultivated in different media and introduced superparamagnetic iron oxide nanoparticles for intracellular labeling and noninvasive tracking of transplanted cells. Our results showed that human embryonic cells and human induced pluripotent cells are able to differentiate towards transplantable neural and neuronal precursors. Our cells can follow the neuroectodermal development described in brain and spinal cord tissue during ontogenesis, which is characterized by the expression of different surface and cytoplasmic markers appearing on distinct levels of neurogenesis. Based on this expression, we defined our pluripotent cell-derived neural precursors as neural stem cells and neural progenitors and defined the most suitable developmental level for neural transplantation. We found a double effect of these transplants in restoring neurological functions; firstly, the neural transplants have a paracrine effect on damaged tissue, which is rapid and transient and, secondly, they have an effect on the...
Stem cells and modified biomaterials in the for the treatment of spinal cord injury
Růžička, Jiří ; Jendelová, Pavla (advisor) ; Sameš, Martin (referee) ; Zvěřina, Eduard (referee)
Progress in experimental treatments of spinal cord injury (SCI) utilizing growth factors, stem cells and biomaterials has revealed the pathological mechanizms of the secondary processes and demonstrated the potential of combined therapy for future clinical treatment. The mobilization of bone marrow by the combined application of Flt3 ligand and G-CSF diminishes astrogliosis and increases axonal sprouting and thus leads to more pronounce spinal tissue sparing and neurological improvement when compared with single treatments. All types of stem cells used in this study significantly decreased the locomotor deficit after SCI. The most noticeable impact was observed in the NP-iPS treated group, especially due to their long term survival, interaction with host tissue, their impact on glial scarring and modulation of the immune response. MSCs, despite their short lifetime, decrease the immune response after SCI and modulate glial scar formation. The lowest effectivity on locomotor recovery after SCI was demonstrated by fetal spinal progenitors, which were not capable of sufficient integration into the host tissue, even though they showed long-term survival and differentiation. The methods used to prepare methacrylate based hydrogels have a significant impact on the adhesion, growth and survival of MSC...
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...
Stem cells in the treatment of spinal cord injury
Juříková, Tereza ; Jendelová, Pavla (advisor) ; Krulová, Magdaléna (referee)
Stem cells are unique thanks to their ability to differentiate into all cell types and self-renewal. They can be used for repairing and functional recovery of various tissues and organs. Regenerative medicine, progressive medical field, use these properties to give a chance to patients with yet incurable health complitations. These include spinal cord injury, which results in huge demyelination and disorders in neurological function. Mesenchymal stem cells contribute to recovery of damaged tissue thanks to its immunomodulatory abilities and production of a number of growth factors. Embryonic stem cells can differentiate into the functional nerve cells, however its use is connected with the posibility of tumorigenesis and also ethical problems. Promising results gives a combinatorial treatment using biomaterials as scaffolds for cells or growth factors. The knowledge of genetic modification of cells will be used in the future. The aim of this thesis is to sumarise current knowledge of the spinal cord treatment with emphasis on tissue specific stem cells. Key words: stem cells - spinal cord injury - tissue recovery - biomaterials

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