Introduction Burns are dynamic wounds that may present a progressive expansion of necrosis into the initially viable zone of stasis. Therefore, salvage of this zone is a major subject of focus in burn research. The beneficial effects of mesenchymal stem cells (MSCs) on the survival of the zone of stasis have been previously documented. However, many gaps still exist in our knowledge regarding the underlying protective mechanisms. Hence, this study was designed to evaluate the pathophysiological basis of MSCs in the prevention of burn wound progression. Methods Wistar rats received thermal trauma on the back according to the “comb burn” model. Animals were randomly divided into sham, control, and stem cell groups with sacrifice and analysis at 72 hours after the burn. The stasis zones were evaluated using histochemistry, immunohistochemistry, biochemistry, real-time polymerase chain reaction assay, and scintigraphy to evaluate the underlying mechanisms. Results Gross evaluation of burn wounds revealed that vital tissue percentage of the zone of stasis was significantly higher in the stem cell group. Semiquantitative grading of the histopathologic findings showed that MSCs alleviated burn-induced histomorphological alterations in the zone of stasis. According to CC3a staining and expression analysis of Bax (B-cell leukemia 2–associated X) and Bcl-2 (B-cell leukemia 2) genes, MSCs attenuated increases in apoptosis postburn. In addition, these transplants showed an immunomodulatory effect that involves reduced neutrophilic infiltration, down-regulation of proinflammatory cytokines (tumor necrosis factor α, interleukin 1β [IL-1β], and IL-6), and up-regulation of the anti-inflammatory cytokine IL-10 in the zone of stasis. Burn-induced oxidative stress was significantly relieved with MSCs, as shown by increased levels of malondialdehyde, whereas the expression and activity of the antioxidant enzyme superoxide dismutase were increased. Finally, MSC-treated interspaces had enhanced vascular density with higher expression levels for vascular endothelial growth factor A, platelet-derived growth factor, fibroblast growth factor, and transforming growth factor β. Gamma camera images documented better tissue perfusion in animals treated with MSCs. Conclusions The protective effects of MSCs are mediated by the inhibition of apoptosis through immunomodulatory, antioxidative, and angiogenic actions.

The recent demonstration using genetic tracing that in the adult pituitary stem cells are normally recruited from the niche in the marginal zone and differentiate into secretory cells in the adenopituitary has elegantly confirmed the proposal made when the pituitary stem cell niche was first discovered 5 years ago. Some of the early controversies have also been resolved. However, many questions remain, such as which are the markers that make a pituitary stem cell truly unique and the exact mechanisms that trigger recruitment from the niche. Little is known about the processes of commitment and differentiation once a stem cell has left the niche. Moreover, the acceptance that pituitary cells are renewed by stem cells implies the existence of regulated mechanisms of cell death in differentiated cells which must themselves be explained. The demonstration of an apoptotic pathway mediated by RET/caspase 3/Pit-1/Arf/p53 in normal somatotrophs is therefore an important step towards understanding how pituitary cell number is regulated. Further work will elucidate how the rates of the three processes of cell renewal, differentiation and apoptosis are balanced in tissue homeostasis after birth, but altered in pituitary hyperplasia in response to physiological stimuli such as puberty and lactation. Thus, we can aim to understand the mechanisms underlying human disease due to insufficient (hypopituitarism) or excess (pituitary tumor) cell numbers.

Objective The aim of our study was to investigate the effect of Transforming growth factor beta-1 (TGF- β 1) gene therapy on the surface markers, multilineage differentiation, viability, apoptosis, cell cycle, DNA damage and senescence of human Dental Pulp-derived Mesenchymal Stromal Cells (hDPSC). Methods hDPSCs were isolated from human teeth, and were cultured with 20% Fetal Bovine Serum (FBS) in minimum essential media-alpha ( α -MEM). TGF- β 1 gene transfer into hDPSCs was performed by electroporation method after the plasmid was prepared. The transfection efficiency was achieved by using western blot and flow cytometry analyses and GFP transfection. Mesenchymal stem cell (MSC) markers, multilineage differentiation, cell proliferation, apoptosis, cell cycle, DNA damage and cellular senescence assays were performed by comparing the transfected and non-transfected cells. Statistical analyses were performed using GraphPad Prism. Results Strong expression of TGF- β 1 in pCMV-TGF- β 1-transfected hDPSCs was detected in flow cytometry analysis. TGF- β 1 transfection efficiency was measured as 95%. Western blot analysis showed that TGF- β 1 protein levels increased at third and sixth days in pCMV-TGF- β 1-transfected hDPSCs. The continuous TGF- β 1 overexpression in hDPSCs did not influence the immunophenotype and surface marker expression of MSCs. Our results showed that TGF- β 1 increased osteogenic and chondrogenic differentiation, but decreased adipogenic differentiation. Overexpression of TGF- β 1 increased the proliferation rate and decreased total apoptosis in hDPSCs (p<0.05). The number of cells at “ S ” phase was higher with TGF- β 1 transfection (p<0.05). Cellular senescence decreased in TGF- β 1 transfected group (p<0.05). Conclusions These results reflect that TGF- β 1 has major impact on MSC differentiation. TGF- β 1 transfection has positive effect on proliferation, cell cycle, and prevents cellular senescence and apoptosis.

Background: Successful limb replantation must be based not only on the viability of the amputated part but also on satisfactory long-term functional recovery. Once the vascular, skeletal, and soft-tissue problems have been taken care of, nerve recovery becomes the ultimate limiting factor. Unfortunately, nerve regeneration after limb replantation is impaired by several consequences. The authors tested the hypothesis that bone marrow mesenchymal stem cells could improve nerve regeneration outcomes in an experimental model of limb replantation. Methods: Twenty rats underwent replantation after total hindlimb amputation. Animals were subdivided into two groups: a replanted but nontreated control group and a replanted and bone marrow mesenchymal stem cell–transplanted group. Three months after surgery, nerve regeneration was assessed using functional, electrophysiologic, histomorphologic, and immunohistochemical analyses. Results: Bone marrow mesenchymal stem cell–treated animals showed significantly better sciatic functional index levels and higher compound muscle action potential amplitudes in comparison with the controls. Histomorphometric analysis revealed that the number of regenerating axons was approximately two-fold greater in the treated nerves. In addition, the mean g-ratio of these axons was within the optimal range. Immunohistochemical assessment revealed that expression of S-100 and myelin basic protein in the treated nerves was significantly higher than in controls. Correspondingly, the expression levels of anti–protein gene product 9.5 and vesicular acetylcholine transporter in motor endplates were also significantly higher. Finally, muscles in the bone marrow mesenchymal stem cell–transplanted group showed significantly larger average fiber areas. Conclusion: The authors’ findings demonstrate that it is possible to improve the degree of nerve regeneration after limb replantation by bone marrow mesenchymal stem cell transplantation.

This study reports the synthesis of three novel axially disubstituted silicon phthalocyanines (1-3-Si) and their quaternized phthalocyanines (1-3-QSi). The resulting compounds were characterized by applying spectroscopic techniques including 1H NMR,...

This study reports the synthesis and characterization of two new mono- and di-substituted phthalonitriles namely 4-((9H-carbazol-3-yl)oxy)-5-chlorophthalonitrile and 4,5-bis((9H-carbazol-3-yl)oxy)phthalonitrile, respectively. Cyclotetramerization of the new phthalonitriles in the presence of zinc (II)...

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