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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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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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Differentiation potential of polydendrocytes after focal cerebral ischemia
Filipová, Marcela ; Anděrová, Miroslava (advisor) ; Jendelová, Pavla (referee)
Ischemic injury leeds to sequence of pathophysiological events, which are accompanied by a release of growth factors and morphogens that significantly affect cell proliferation, migration and also their differentiation. Following ischemia, besides enhanced neurogenesis and gliogenesis in subventricular zone of the lateral ventricles and gyrus dentatus of the hippocampus, neurogenesis/gliogenesis also occurs in non-neurogenic regions, such as cortex or striatum. Recently, the attention was turned to a new glial cell type, termed polydendrocytes or NG2 glia. Under physiological conditions, these cells are able to divide and differentiate into mature oligodendrocytes due to they have often been equated with oligodendrocyte precursor cells. Based on recent reports, polydendrocytes are also able to generate protoplasmic astrocytes (Zhu et al., 2008) and neurons in vitro (Belachew et al., 2003), however their ability to differentiate into astrocytes or neurons under physiological or pathological conditions is still highly debated. Therefore, we have investigated the effect of different growth factors and morphogens, specifically brain-derived neurotrophic factor (BDNF), basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF) and a morphogen sonic hedgehog (Shh), on...
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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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Molecular mechanisms regulating participation of neural crest on developmental processes and homeostasis in selected localizations
Krejčí, Eliška ; Grim, Miloš (advisor) ; Hampl, Aleš (referee) ; Jendelová, Pavla (referee)
This PhD thesis focuses on the study of neural crest (NC) properties and mechanisms regulating its development. It is based on four original papers, two of which are wholy concerning NC. In the first project we showed that transcription factor C-MYB is expressed in majority of cells in the developing chick embryo. Its expression level is elevated in neural folds and migrating NC cells. Other experiments showed that this elevated level of intracellular c-Myb influences induction and epithelial-mesenchymal transformation of NC cells, and that c-Myb lies within the BMP4 signalling cascade. In the second project we explored the spatio-temporal specification along the antero-posterior axis of the limb bud - a mechanism significantly regulating also NC development. We showed that deletion of regulatory element of Plzf transcription repressor gene caused decrease of Plzf expression in the limb buds followed by anterior expansion of its downstream genes (Hoxd10-13) expression domains only in the hind limb, with a resulting additional finger. The third paper studies developmental origin of medial border of mammalian scapula. We showed that its cells originate from somites and not in NC. In the last project we studied NC stem cells isolated from human adult hair follicles. These cells express NC stem cell...
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název v anglickém jazyce není uveden
Kříž, Jan ; Saudek, František (advisor) ; Jendelová, Pavla (referee) ; Haluzík, Martin (referee)
Islet transplantation represents an alternative approach in the treatment of patients with type-1 diabetes mellitus. It makes possible to give insulin-producing tissue to patients, which could not underwent surgery operative due to ill health. The second benefit of tissue transplantation is utilization of pancreases unsuitable for organ transplantation in term of surgical criteria. The dissertation includes two studies focused on study of some problems of islet transplantation. In the first study was tested a new method for induction of microchimerism by bone marrow transplantation and its effect on islet allograft survival. We reported, that short-term tacrolimus therapy significantly prolonged insulin independence in fully allogeneic rat model even if the immunosupresants were discontinued. Conditioning of recipients with bone marrow cells transplantation had not additional effect. In the second study there is presented an approach for imaging of intrahepatally-sited islets. The technique is based on labeling of islets by non-toxic superparamagnetic agent during two day culture. After transplantation islets are imaged as hypointense spots on T2 weighing magnetic resonance sections in both in vitro and in vivo experiments. Outstanding changes in MR images were demonstrated during acute rejection of...
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