Myeloproliferativní neoplázie (MPN) jsou klonální poruchy, které vznikají na úrovni hematopoetických kmenových buněk. Somatické mutace, jako např. JAK2V617F, lze nalézt u purifikovaných hematopoetických kmenových buněk a jejich potomstva. Nicméně je možné objevit výrazné interindividuální rozdíly v mutantní alelické zátěži u zralých krvinek pacienta a v počtu hematopoetických linií, které jsou zasažené. Ne všichni pacienti s MPN vykazují přítomnost klonálních markerů u B lymfocytů a T buňky jsou téměř vždy vyloučeny. U mnoha pacientů s MPN je možné objevit více než jednu somatickou mutaci a pořadí, v němž se tyto mutace objevují, se může u jednotlivých pacientů lišit. Myší modely ukázaly, že MPN může být iniciována JAK2V617F bez přítomnosti dalších mutací. Všechny dosavadní myší modely jsou však založeny na polyklonálním onemocnění. Za účelem navržení lepších léčebných postupů a potažmo i vyléčení MPN bude důležité pochopit časné kroky při iniciaci choroby., Myeloproliferative neoplasms (MPN) are clonal disorders that originate at the level of hematopoietic stem cells. Somatic mutations such as JAK2V617F can be found in purified hematopoietic stem cells and their progeny. Nevertheless, large inter-individual differences in the mutant allele burden in the patient’s mature blood cells and in the number of hematopoietic lineages that are involved can be found. Not all patients with MPN show presence of clonality markers in B lymphocytes and T cells are almost always excluded. In many MPN patients more than one somatic mutation can be found and the order in which these mutations occur can vary between individual patients. Mouse models have shown that MPN can be initiated by JAK2V617F without the presence of additional mutations. However, all mouse models to date are based on polyclonal disease. Understanding the early steps in disease initiation will be important for designing better strategies for the treatment and ultimately cure of MPN, Radek C. Skoda, and Literatura 50
Stem cells biology is one of the most frequent topic of physiological research of today. Spinal fusion represents common bone biology challenge. It is the indicator of osteoinduction and new bone formation on ectopic model. The purpose of this study was to establish a simple model of spinal fusion based on a rat model including verification of the possible use of titanium microplates with hydroxyapatite scaffold combined with human bone marrow-derived mesenchymal stem cells (MSCs). Spinous processes of two adjacent vertebrae were fixed in 15 Wistar rats. The space between bony vertebral arches and spinous processes was either filled with augmentation material only and covered with a resorbable collagen membrane (Group 1), or filled with augmentation material loaded with 5 × 10 6 MSCs and covered with a resorbable collagen membrane (Group 2). The rats were sacrificed 8 weeks after the surgery. Histology, histomorphometry and micro-CT were performed. The new model of interspinous fusion was safe, easy, inexpensive, with zero mortality. We did not detect any substantial pathological changes or tumor formation after graft implantation. We observed a nonsignificant effect on the formation of new bone tissue between Group 1 and Group 2. In the group with MSCs (Group 2) we described mino r inflamatory response which indicates the imunomodulational and antiinflamatory role of MSCs. In conclusion, this new model proved to be easy to use in small animals like rats., K. Klíma, V. Vaněček, A. Kohout, O. Jiroušek, R. Foltán, J. Štulík, V. Machoň, G. Pavlíková, P. Jendelová, E. Syková, J. Šedý., and Obsahuje bibliografii