Kmenové buňky pro své jedinečné vlastnosti – plasticitu, slibují všestranné využití, zejména možnostireparace většiny orgánů a tkání lidského těla – buněčná terapie. Autoři ve svémsdělení prezentují svojeexperimentální výsledky na modelu neurálních kmenových buněk (NSCs). Hlavním cílem je průkazzachování hemopoetické identity NSCs. Subletálně celotělově ozářené myši dávkou LD 8,5 Gy bylyzachráněné transplantací značených (X-Gal+) NSCs. Průkaz zvýšeného záchytu NSCs ve slezině násvedlo k myšlence hledání vztahu hemopoetického mikroprostředí a hemopoetické identity. Průkazzachování hemopoetické identity byl proveden pomocí kultivace CFU-GM z kostní dřeně – kde bylyidentifikovány buňky vykazující X-Gal pozitivitu (stanovení těchto buněk bylo provedeno pomocíhistochemického testu). Naše experimenty poukazují na různé možnosti, jak transplantace NSCs můžeovlivnit poškozenou hematopoézu.

Stem cells for their unique property - plasticity promise a universal utilization,mainly, in the reparationof most organs and tissues in the human body. In this communication, the authors presents theirexperimental results in a model of neural stem cells (NCSc) where the main goal was to preserve theNSCs hemopoietic identity. Mice given whole body sublethal irradiation with a dose of LD 8.5 Gy weresaved by transplantation of labelled (X-Gal+) NSCs. The demonstration of increased uptake of NSCs inthe spleen led us to study the relationship of hemopoietic microenvironment and hemopoietic identity.The proof of hemopoeitic identity was performed by cultivation of CFU-GM from the bone marrow -where cells exhibiting X-Gal positivity were identified by histochemistry. Our experiments showdifferent ways how NSCs transplantation may influence the damaged hematopoiesis.

• MeSH
• dávka záření MeSH
• finanční podpora výzkumu jako téma MeSH
• hematopoéza MeSH
• kmenové buňky fyziologie   MeSH
• kostní dřeň MeSH
• kultivované buňky MeSH
• modely u zvířat MeSH
• myši MeSH
• transplantace kostní dřeně MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• přehledy MeSH
• srovnávací studie MeSH

• MeSH
• buněčná diferenciace MeSH
• histocytochemie metody   MeSH
• kmenové buňky MeSH
• kultivované buňky MeSH
• nervový systém embryologie   MeSH

Human embryonic stem cell-derived neural precursors (hESC NPs) are considered to be a promising tool for cell-based therapy in central nervous system injuries and neurodegenerative diseases. The Ca(2+) ion is an important intracellular messenger essential for the regulation of various cellular functions. We investigated the role and physiology of Ca(2+) signaling to characterize the functional properties of CCTL14 hESC NPs during long-term maintenance in culture (in vitro). We analyzed changes in cytoplasmic Ca(2+) concentration ([Ca(2+)]i) evoked by high K(+), adenosine-5'-triphosphate (ATP), glutamate, γ-aminobutyric acid (GABA), and caffeine in correlation with the expression of various neuronal markers in different passages (P6 through P10) during the course of hESC differentiation. We found that only differentiated NPs from P7 exhibited significant and specific [Ca(2+)]i responses to various stimuli. About 31% of neuronal-like P7 NPs exhibited spontaneous [Ca(2+)]i oscillations. Pharmacological and immunocytochemical assays revealed that P7 NPs express L- and P/Q-type Ca(2+) channels, P2X2, P2X3, P2X7, and P2Y purinoreceptors, glutamate receptors, and ryanodine (RyR1 and RyR3) receptors. The ATP- and glutamate-induced [Ca(2+)]i responses were concentration-dependent. Higher glutamate concentrations (over 100 μM) caused cell death. Responses to ATP were observed in the presence or in the absence of extracellular Ca(2+). These results emphasize the notion that with time in culture, these cells attain a transient period of operative Ca(2+) signaling that is predictive of their ability to act as stem elements.

• MeSH
• biologické markery metabolismus   MeSH
• buněčná diferenciace účinky léků   MeSH
• časové faktory MeSH
• embryonální kmenové buňky cytologie   účinky léků   metabolismus   MeSH
• glutamáty farmakologie   MeSH
• intracelulární prostor účinky léků   metabolismus   MeSH
• konfokální mikroskopie MeSH
• lidé MeSH
• nervové kmenové buňky cytologie   účinky léků   metabolismus   MeSH
• počet buněk MeSH
• purinergní receptory metabolismus   MeSH
• vápník metabolismus   MeSH
• vápníková signalizace * účinky léků   MeSH
• vápníkové kanály metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• neuroplasticita MeSH
• poranění nervového systému rehabilitace   MeSH
• regenerace nervu MeSH
• rehabilitace MeSH
• Publikační typ
• monografie MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• neurologie
• traumatologie
• neurochirurgie

A promising therapeutic strategy for amyotrophic lateral sclerosis (ALS) treatment is stem cell therapy. Neural progenitors derived from induced pluripotent cells (NP-iPS) might rescue or replace dying motoneurons (MNs). However, the mechanisms responsible for the beneficial effect are not fully understood. The aim here was to investigate the mechanism by studying the effect of intraspinally injected NP-iPS into asymptomatic and early symptomatic superoxide dismutase (SOD)1G93A transgenic rats. Prior to transplantation, NP-iPS were characterized in vitro for their ability to differentiate into a neuronal phenotype. Motor functions were tested in all animals, and the tissue was analyzed by immunohistochemistry, qPCR, and Western blot. NP-iPS transplantation significantly preserved MNs, slowed disease progression, and extended the survival of all treated animals. The dysregulation of spinal chondroitin sulfate proteoglycans was observed in SOD1G93A rats at the terminal stage. NP-iPS application led to normalized host genes expression (versican, has-1, tenascin-R, ngf, igf-1, bdnf, bax, bcl-2, and casp-3) and the protection of perineuronal nets around the preserved MNs. In the host spinal cord, transplanted cells remained as progenitors, many in contact with MNs, but they did not differentiate. The findings suggest that NP-iPS demonstrate neuroprotective properties by regulating local gene expression and regulate plasticity by modulating the central nervous system (CNS) extracellular matrix such as perineuronal nets (PNNs).

• MeSH
• amyotrofická laterální skleróza terapie   MeSH
• indukované pluripotentní kmenové buňky cytologie   MeSH
• krysa rodu rattus MeSH
• kultivované buňky MeSH
• lidé MeSH
• nervové kmenové buňky cytologie   metabolismus   transplantace   MeSH
• neuroplasticita * MeSH
• neurotrofní faktory genetika   metabolismus   MeSH
• periferní nervy fyziologie   MeSH
• potkani Sprague-Dawley MeSH
• proteiny regulující apoptózu genetika   metabolismus   MeSH
• regenerace nervu MeSH
• tenascin genetika   metabolismus   MeSH
• transplantace kmenových buněk metody   MeSH
• versikany genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• lidé MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

The ongoing process of neurogenesis in the adult mammalian forebrain suggests the possible capacity for limited self-repair after brain injury. Previously, we have demonstrated that in an animal model of Huntington's disease the neurodegenerative process initiates immediate intensive cell proliferation and differentiation resulting in characteristic enlargement of the subependymal zone (SEZ) of lateral brain ventricles. Now, our interest is focused on the architecture of the neurogenic niche of the SEZ in the identical model, particularly on characteristic features of astrocyte-like cells which are considered to be not only niche cells but also neural stem cells. Our findings prove higher activation of the lateral part of the SEZ (L-SEZ) adjacent to the degenerated striatum compared with the rostral part of the SEZ (R-SEZ). In the activated L-SEZ, niche cells which ensheathe clusters of neural progenitors are of immature astrocytic phenotype because of nestin and vimentin expression (except the expression of glial fibrillary acidic protein). However, the coexpression of all three filaments is not always found. Intermediate filaments also enable us to distinguish the basic shape of astrocytic cells within the SEZ, majority of which resemble protoplasmic rather than fibrillary astrocytes. Furthermore, our results show a wide plasticity of these astrocyte-like cells in immediate response to an extensive pathological process in the brain. These observations are consistent with the fact that adult stem cells undergo different processes in an already mature environment, and therefore can exhibit some specific characteristics unlike the embryonic or fetal neural stem cells. Copyright (c) 2006 S. Karger AG, Basel.

• MeSH
• buněčná diferenciace fyziologie   MeSH
• buněčné dělení fyziologie   MeSH
• corpus striatum fyziologie   MeSH
• dospělí MeSH
• financování organizované MeSH
• Huntingtonova nemoc patologie   MeSH
• kmenové buňky cytologie   MeSH
• lidé MeSH
• neurony cytologie   MeSH
• zvířata MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• přehledy MeSH

Neural stem cells are fundamental to development of the central nervous system (CNS)-as well as its plasticity and regeneration-and represent a potential tool for neuro transplantation therapy and research. This study is focused on examination of the proliferation dynamic and fate of embryonic neural stem cells (eNSCs) under differentiating conditions. In this work, we analyzed eNSCs differentiating alone and in the presence of sonic hedgehog (SHH) or triiodothyronine (T3) which play an important role in the development of the CNS. We found that inhibition of the SHH pathway and activation of the T3 pathway increased cellular health and survival of differentiating eNSCs. In addition, T3 was able to increase the expression of the gene for the receptor smoothened (Smo), which is part of the SHH signaling cascade, while SHH increased the expression of the T3 receptor beta gene (Thrb). This might be the reason why the combination of SHH and T3 increased the expression of the thyroxine 5-deiodinase type III gene (Dio3), which inhibits T3 activity, which in turn affects cellular health and proliferation activity of eNSCs.

• MeSH
• jodidperoxidasa genetika   metabolismus   MeSH
• kultivované buňky MeSH
• myší embryonální kmenové buňky cytologie   metabolismus   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• nervové kmenové buňky cytologie   metabolismus   MeSH
• neurogeneze * MeSH
• proteiny hedgehog genetika   metabolismus   MeSH
• receptor Smoothened genetika   metabolismus   MeSH
• trijodthyronin metabolismus   MeSH
• tyreoidální hormony, receptory beta genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Glial cells expressing neuron-glial antigen 2 (NG2), also known as oligodendrocyte progenitor cells (OPCs), play a critical role in maintaining brain health. However, their ability to differentiate after ischemic injury is poorly understood. The aim of this study was to investigate the properties and functions of NG2 glia in the ischemic brain. Using transgenic mice, we selectively labeled NG2-expressing cells and their progeny in both healthy brain and after focal cerebral ischemia (FCI). Using single-cell RNA sequencing, we classified the labeled glial cells into five distinct subpopulations based on their gene expression patterns. Additionally, we examined the membrane properties of these cells using the patch-clamp technique. Of the identified subpopulations, three were identified as OPCs, whereas the fourth subpopulation had characteristics indicative of cells likely to develop into oligodendrocytes. The fifth subpopulation of NG2 glia showed astrocytic markers and had similarities to neural progenitor cells. Interestingly, this subpopulation was present in both healthy and post-ischemic tissue; however, its gene expression profile changed after ischemia, with increased numbers of genes related to neurogenesis. Immunohistochemical analysis confirmed the temporal expression of neurogenic genes and showed an increased presence of NG2 cells positive for Purkinje cell protein-4 at the periphery of the ischemic lesion 12 days after FCI, as well as NeuN-positive NG2 cells 28 and 60 days after injury. These results suggest the potential development of neuron-like cells arising from NG2 glia in the ischemic tissue. Our study provides insights into the plasticity of NG2 glia and their capacity for neurogenesis after stroke.

• MeSH
• antigeny metabolismus   MeSH
• astrocyty metabolismus   MeSH
• ischemie mozku * metabolismus   MeSH
• mozek metabolismus   MeSH
• myši transgenní MeSH
• myši MeSH
• nervové kmenové buňky * metabolismus   MeSH
• neuroglie metabolismus   MeSH
• oligodendroglie metabolismus   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• biologie buňky MeSH
• cytokineze MeSH
• mikroskopie MeSH
• pohyb buněk MeSH
• Publikační typ
• abstrakt z konference MeSH
• sborníky MeSH

• Konspekt
• Buněčná biologie. Cytologie
• NLK Obory
• biologie
• cytologie, klinická cytologie
• radiologie, nukleární medicína a zobrazovací metody
• histologie

BACKGROUND: Lipopolysaccharide (LPS)-induced inflammation of lung tissues triggers irreversible alterations in the lung parenchyma, leading to fibrosis and pulmonary dysfunction. While the molecular and cellular responses of immune and connective tissue cells in the lungs are well characterized, the specific epithelial response remains unclear due to the lack of representative cell models. Recently, we introduced human embryonic stem cell-derived expandable lung epithelial (ELEP) cells as a novel model for studying lung injury and regeneration. METHODS: ELEPs were derived from the CCTL 14 human embryonic stem cell line through activin A-mediated endoderm specification, followed by further induction toward pulmonary epithelium using FGF2 and EGF. ELEPs exhibit a high proliferation rate and express key structural and molecular markers of alveolar progenitors, such as NKX2-1. The effects of Escherichia coli LPS serotype O55:B5 on the phenotype and molecular signaling of ELEPs were analyzed using viability and migration assays, mRNA and protein levels were determined by qRT-PCR, western blotting, and immunofluorescent microscopy. RESULTS: We demonstrated that purified LPS induces features of a hybrid epithelial-to-mesenchymal transition in pluripotent stem cell-derived ELEPs, triggers the unfolded protein response, and upregulates intracellular β-catenin level through retention of E-cadherin within the endoplasmic reticulum. CONCLUSIONS: Human embryonic stem cell-derived ELEPs provide a biologically relevant, non-cancerous lung cell model to investigate molecular responses to inflammatory stimuli and address epithelial plasticity. This approach offers novel insights into the fine molecular processes underlying lung injury and repair.

• MeSH
• buněčné linie MeSH
• CD antigeny metabolismus   MeSH
• endoplazmatické retikulum * metabolismus   účinky léků   MeSH
• epitelo-mezenchymální tranzice * účinky léků   MeSH
• epitelové buňky * účinky léků   metabolismus   cytologie   MeSH
• kadheriny * metabolismus   MeSH
• lidé MeSH
• lidské embryonální kmenové buňky * cytologie   MeSH
• lipopolysacharidy * farmakologie   MeSH
• plíce * cytologie   MeSH
• tyreoidální jaderný faktor 1 MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH