Mesenchymal stem cells have shown regenerative properties in many tissues. This feature had originally been ascribed to their multipotency and thus their ability to differentiate into tissue-specific ...cells. However, many researchers consider the secretome of mesenchymal stem cells the most important player in the observed reparative effects of these cells. In this review, we specifically focus on the potential neuroregenerative effect of mesenchymal stem cells, summarize several possible mechanisms of neuroregeneration and list key factors mediating this effect. We illustrate examples of mesenchymal stem cell treatment in central nervous system disorders including stroke, neurodegenerative disorders (such as Parkinson's disease, Huntington's disease, multiple system atrophy and cerebellar ataxia) and inflammatory disease (such as multiple sclerosis). We specifically highlight studies where mesenchymal stem cells have entered clinical trials.
•We review evidence for the perivascular location of mesenchymal stem cells.•We emphasize new findings of mesenchymal stem cells in the perivascular niche in the adult brain.•We review the different mechanisms how mesenchymal stem cells contribute to neuroregeneration.•We summarize clinical trials performed in CNS disorders using mesenchymal stem cells.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Blood vessels and adjacent cells form perivascular stem cell niches in adult tissues. In this perivascular niche, a stem cell with mesenchymal characteristics was recently identified in some adult ...somatic tissues. These cells are pericytes that line the microvasculature, express mesenchymal markers and differentiate into mesodermal lineages but might even have the capacity to generate tissue-specific cell types. Here, we isolated, purified and characterized a previously unrecognized progenitor population from two different regions in the adult human brain, the ventricular wall and the neocortex. We show that these cells co-express markers for mesenchymal stem cells and pericytes in vivo and in vitro, but do not express glial, neuronal progenitor, hematopoietic, endothelial or microglial markers in their native state. Furthermore, we demonstrate at a clonal level that these progenitors have true multilineage potential towards both, the mesodermal and neuroectodermal phenotype. They can be epigenetically induced in vitro into adipocytes, chondroblasts and osteoblasts but also into glial cells and immature neurons. This progenitor population exhibits long-term proliferation, karyotype stability and retention of phenotype and multipotency following extensive propagation. Thus, we provide evidence that the vascular niche in the adult human brain harbors a novel progenitor with multilineage capacity that appears to represent mesenchymal stem cells and is different from any previously described human neural stem cell. Future studies will elucidate whether these cells may play a role for disease or may represent a reservoir that can be exploited in efforts to repair the diseased human brain.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Boundary conditions required for numerical solution of the Boltzmann kinetic equation (BKE) for mass/heat transfer between evaporation and condensation surfaces are analyzed by comparison of BKE ...results with molecular dynamics (MD) simulations. Lennard–Jones potential with parameters corresponding to solid argon is used to simulate evaporation from the hot side, nonequilibrium vapor flow with a Knudsen number of about 0.02, and condensation on the cold side of the condensed phase. The equilibrium density of vapor obtained in MD simulation of phase coexistence is used in BKE calculations for consistency of BKE results with MD data. The collision cross-section is also adjusted to provide a thermal flux in vapor identical to that in MD. Our MD simulations of evaporation toward a nonreflective absorbing boundary show that the velocity distribution function (VDF) of evaporated atoms has the nearly semi-Maxwellian shape because the binding energy of atoms evaporated from the interphase layer between bulk phase and vapor is much smaller than the cohesive energy in the condensed phase. Indeed, the calculated temperature and density profiles within the interphase layer indicate that the averaged kinetic energy of atoms remains near-constant with decreasing density almost until the interphase edge. Using consistent BKE and MD methods, the profiles of gas density, mass velocity, and temperatures together with VDFs in a gap of many mean free paths between the evaporation and condensation surfaces are obtained and compared. We demonstrate that the best fit of BKE results with MD simulations can be achieved with the evaporation and condensation coefficients both close to unity.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
The effect of the pineal indole hormone melatonin on the life span of mice, rats and fruit flies has been studied using various approaches. It has been observed that in female CBA, SHR, SAM and ...transgenic HER-2/neu mice long-term administration of melatonin was followed by an increase in the mean life span. In rats, melatonin treatment increased survival of male and female rats. In
D. melanogaster, supplementation of melatonin to nutrient medium during developmental stages produced contradictory results, but and increase in the longevity of fruit flies has been observed when melatonin was added to food throughout the life span. In mice and rats, melatonin is a potent antioxidant both in vitro and in vivo. Melatonin alone turned out neither toxic nor mutagenic in the Ames test and revealed clastogenic activity at high concentration in the COMET assay. Melatonin has inhibited mutagenesis and clastogenic effect of a number of indirect chemical mutagens. Melatonin inhibits the development of spontaneous and 7-12-dimethlbenz(a)anthracene (DMBA)- or N-nitrosomethylurea-induced mammary carcinogenesis in rodents; colon carcinogenesis induced by 1,2-dimethylhydrazine in rats, N-diethylnitrosamine-induced hepatocarcinogenesis in rats, DMBA-induced carcinogenesis of the uterine cervix and vagina in mice; benzo(a)pyrene-induced soft tissue carcinogenesis and lung carcinogenesis induced by urethan in mice. To identify molecular events regulated by melatonin, gene expression profiles were studied in the heart and brain of melatonin-treated CBA mice using cDNA gene expression arrays (15,247 and 16,897 cDNA clone sets, respectively). It was shown that genes controlling the cell cycle, cell/organism defense, protein expression and transport are the primary effectors for melatonin. Melatonin also increased the expression of some mitochondrial genes (16S, cytochrome
c oxidases 1 and 3 (COX1 and COX3), and NADH dehydrogenases 1 and 4 (ND1 and ND4)), which agrees with its ability to inhibit free radical processes. Of great interest is the effect of melatonin upon the expression of a large number of genes related to calcium exchange, such as Cul5, Dcamkl1 and Kcnn4; a significant effect of melatonin on the expression of some oncogenesis-related genes was also detected. Thus, we believe that melatonin may be used for the prevention of premature aging and carcinogenesis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Human embryonic stem cells (hESCs) have been proposed as a source of dopamine (DA) neurons for transplantation in Parkinson's disease (PD). We have investigated the effect of in vitro ...predifferentiation on in vivo survival and differentiation of hESCs implanted into the 6‐OHDA (6‐hydroxydopamine)‐lesion rat model of PD. The hESCs were cocultured with PA6 cells for 16, 20, or 23 days, leading to the in vitro differentiation into DA neurons. Grafted hESC‐derived cells survived well and expressed neuronal markers. However, very few exhibited a DA neuron phenotype. Reversal of lesion‐induced motor deficits was not observed. Rats grafted with hESCs predifferentiated in vitro for 16 days developed severe teratomas, whereas most rats grafted with hESCs predifferentiated for 20 and 23 days remained healthy until the end of the experiment. This indicates that prolonged in vitro differentiation of hESCs is essential for preventing formation of teratomas.
A number of molecular methods of gene expression analysis can approach genomic level. Among those, Serial Analysis of Gene Expression (SAGE) stands out. Unlike many other techniques, SAGE allows both ...qualitative and quantitative analysis of previously unknown transcripts. Over the course of the last 13 years, SAGE has became a recognized tool of large-scale gene expression profiling, being used extensively in human, animal, yeast and plant studies of various nature. A number of important adaptations was introduced both to the protocol of SAGE library construction and to the analytical algorithm employed. Moreover, some variations of the original protocol (MAGE, SADE, microSAGE, miniSAGE, longSAGE, superSAGE, deepSAGE, etc.) were derived to improve the utility of SAGE in certain conditions. Current review aims comparing the benefits and drawbacks of the techniques for high-throughput gene expression analysis (including SAGE) in a realistic, balanced manner. Issues related to modifications to the original protocol and further development of the SAGE are discussed.
Bone marrow (BM) and subcutaneous adipose tissue (Ad) are both considered being prospective sources of MSC for therapeutic applications. However, functional properties and therapeutic efficacy of MSC ...derived from different tissues of the same patient are still poorly investigated. In our study, BM-MSC and F-MSC cultures from 43 adult donors were evaluated in successive passages for immunophenotype, secretion of VEGF, SDF1, MCP1, IL6 and TGFβ1, frequency of colony-forming units (CFU-F), frequency of adipo- and osteo-progenitors (CFU-Ad, CFU-Ost), and for onset of in vitro replicative senescence. We have demonstrated that at early passages (P2-P4 or up to 14-15 in vitro population doublings) BM- and Ad- derived MSC cultures are comparable in such important characteristics as proliferation rate (population doubling time: 3,4±0,2% in BM-MSC, 3±0,3 % in F-MSC), clonogenity (CFU-F frequency: 32±5% in BM-MSC, 31±5% in F-MSC), differentiation potential (CFU-Ad frequency: 10,4±2% in BM-MSC, 13±3% in F-MSC; CFU-Ost frequency: 18,5±5,5% in BM-MSC, 18±5% in F-MSC), but differ significantly in abundance of CD146+ fraction within the sample (25±5% in BM-MSC, 7±3 % in F-MSC) and in a level of VEGF, SDF-1, MCP1 and TGFβ1 secretion. We have also demonstrated that BM-MSC enter senescence after P3-4 while most of F-MSC did not show senescence features up to P6-8. Together, these data demonstrate that specific properties of MSC from different sources should be always taken into account, when developing and optimizing the specific protocols for MSC expansion and evaluation for each particular clinical application.
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BFBNIB, GIS, IJS, KISLJ, NUK, PNG, UL, UM, UPUK
•A numerical study of counter-flow evaporative exchangers is presented.•The ɛ-NTU model is used for the analysis.•Different arrangements of air coolers were compared.•Additionally selected ...operational aspects were tested.
This paper numerically investigates the performance and heat and mass transfer processes that occur in counter-flow indirect evaporative air coolers. Different types of counter-flow air coolers were compared: a typical counter-flow unit, the same unit operating as a heat recovery exchanger, a regenerative unit and a novel modified exchanger, proposed by authors. Additionally the paper investigated impact of location of the perforated holes in the channel plate of regenerative air cooler. The numerical model is based on a one-dimensional heat and mass transfer analysis that was validated against existing experimental data. The results obtained from the simulation reveal the high effectiveness of the presented units. It was established that selected arrangements of the presented exchangers are characterized by the different efficiency in different air-conditioning applications.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Due to the chaotic motion of charged particles carried by turbulent eddies, electrical quantities in the atmospheric boundary layer (ABL) have short-term variability superimposed on long-term ...variability caused by sources from regional to global scales. In this study the influence of radon exhalation rate, aerosol distribution and turbulent transport efficiency on the variability of fair-weather atmospheric electricity is investigated via Lagrangian stochastic modelling. For the mid-latitude lower atmosphere undisturbed by precipitation, electrified clouds, or thunderstorms, the model is capable of reproducing the diurnal variation in atmospheric electrical parameters detected by ground-based measurements. Based on the analysis of field observations and numerical simulation it is found that the development of the convective boundary layer, accompanied by an increase in turbulent kinetic energy, forms the vertical distribution of radon and its decaying short-lived daughters to be approximately coincident with the barometric law for several eddy turnover times. In the daytime ABL the vertical distribution of atmospheric electrical conductivity tends to be uniform except within the surface layer, due to convective mixing of radon and its radioactive decay products. At the same time, a decrease in the conductivity near the ground is usually observed. This effect leads to an enhanced ground-level atmospheric electric field compared to that normally observed in the nocturnal stably-stratified boundary layer. The simulation showed that the variability of atmospheric electric field in the ABL associated with internal origins is significant in comparison to the variability related to changes in global parameters. It is suggested that vertical profiles of electrical quantities can serve as informative parameters on ABL turbulent dynamics and can even more broadly characterize the state of the environment.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Early initiation of enteral feeding is recognized to play a crucial role in improving the outcomes of treatment of acute pancreatitis. However, the method of administration of enteral nutrition ...remains debatable. We present the experience of treating a patient with moderate-severe acute pancreatitis, at high risk of progressing to a severe or fatal condition, using a novel method of selective feeding with duodenal isolation.
A 27-year-old female patient presented to the emergency unit of the hospital with a typical manifestation of acute pancreatitis. Despite a conventional treatment, the patient's condition deteriorated by day 2 of hospitalization. Using an endoscopic approach, a novel catheter PandiCath
was placed to the duodenum of the patient, isolating its segment between the duodenal bulb and the ligament of Treitz. In the isolated area created, a negative pressure was applied, followed by introduction of early selective enteral feeding. The patient's condition subsequently improved in a rapid manner, and no complications often associated with moderate-to-severe acute pancreatitis developed.
Within 48 h of starting treatment with the novel method, it can prevent the development of multiple organ failure and, when combined with minimally invasive drainage methods, help prevent infection.
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