RESUMO
Austenitic stainless steel is a vital material in various industries, with excellent heat and corrosion resistance, and is widely used in high-temperature environments as a component for internal combustion engines of transportation vehicles or power plant piping. These components or structures are required to be durable against severe load conditions and oxidation damage in high-temperature environments during their service life. In this regard, in particular, oxidation damage and fatigue life are very important influencing factors, while existing studies have focused on materials and fracture behavior. In order to ensure the fatigue life of austenitic stainless steel, therefore, it is necessary to understand the characteristics of the fracture process with microstructural change including oxidation damage according to the temperature condition. In this work, low-cycle fatigue tests were performed at various temperatures to determine the oxidation damage together with the fatigue life of austenitic stainless steel containing niobium. The characteristics of oxidation damage were analyzed through microstructure observations including scanning electron microscope, energy-dispersive X-ray spectroscopy, and the X-ray diffraction patterns. In addition, a unified low-cycle fatigue life model coupled with the fracture mechanism-based lifetime and the Neu-Sehitoglu model for considering the influence of damage by oxidation was proposed. After the low-cycle fatigue tests at temperatures of 200-800 °C and strain amplitudes of 0.4% and 0.5%, the accuracy of the proposed model was verified by comparing the test results with the predicted fatigue life, and the validity by using the oxidation damage parameters for Mar-M247 was confirmed through sensitivity analysis of the parameters applied in the oxidation damage model. As a result, the average thickness of the oxide layer and the penetration length of the oxide intrusion were predicted with a mean error range of 14.7% and 13%, respectively, and the low-cycle fatigue life was predicted with a ±2 factor accuracy at the measurement temperatures under all experimental conditions.
RESUMO
Mesenchymal stem cells (MSCs) are one of the most extensively studied stem cell types owing to their capacity for differentiation into multiple lineages as well as their ability to secrete regenerative factors and modulate immune functions. However, issues remain regarding their further application for cell therapy. Here, to demonstrate the superiority of the improvement of MSCs, we divided umbilical cord blood-derived MSCs (UCB-MSCs) from 15 donors into two groups based on efficacy and revealed donor-dependent variations in the anti-inflammatory effect of MSCs on macrophages as well as their immunoregulatory effect on T cells. Through surface marker analyses (242 antibodies), we found that HLA-A2 was positively related to the anti-inflammatory and immunoregulatory function of MSCs. Additionally, HLA-A2 mRNA silencing in MSCs attenuated their therapeutic effects in vitro; namely, the suppression of LPS-stimulated macrophages and phytohemagglutinin-stimulated T cells. Moreover, HLA-A2 silencing in MSCs significantly decreased their therapeutic effects in a rat model of hyperoxic lung damage. The present study provides novel insights into the quality control of donor-derived MSCs for the treatment of inflammatory conditions and diseases.
RESUMO
Stem cell therapy is a promising option for treating functional deficits in the stroke-damaged brain. Induced pluripotent stem cells (iPSCs) are attractive sources for cell therapy as they can be efficiently differentiated into neural lineages. Episomal plasmids (EPs) containing reprogramming factors can induce nonviral, integration-free iPSCs. Thus, iPSCs generated by an EP-based reprogramming technique (ep-iPSCs) have an advantage over gene-integrating iPSCs for clinical applications. However, there are few studies regarding the in vivo efficacy of ep-iPSCs. In this study, we investigated the therapeutic potential of intracerebral transplantation of neural precursor cells differentiated from ep-iPSCs (ep-iPSC-NPCs) in a rodent stroke model. The ep-iPSC-NPCs were transplanted intracerebrally in a peri-infarct area in a rodent stroke model. Rats transplanted with fibroblasts and vehicle were used as controls. The ep-iPSC-NPC-transplanted animals exhibited functional improvements in behavioral and electrophysiological tests. A small proportion of ep-iPSC-NPCs were detected up to 12 weeks after transplantation and were differentiated into both neuronal and glial lineages. In addition, transplanted cells promoted endogenous brain repair, presumably via increased subventricular zone neurogenesis, and reduced poststroke inflammation and glial scar formation. Taken together, these results strongly suggest that intracerebral transplantation of ep-iPSC-NPCs is a useful therapeutic option to treat clinical stroke through multimodal therapeutic mechanisms.
RESUMO
BACKGROUND: Mesenchymal stem cells (MSCs) have broad-spectrum therapeutic effects in various diseases, and thus have many clinical applications. However, it is difficult to produce sufficient numbers of MSCs for clinical use, and improved culture systems are required. Here, we report the effects of calcium (Ca2+) and hypoxia on the proliferation of human umbilical cord blood-derived MSCs (hUCB-MSCs). In addition, we determined the optimal conditions of these two factors for the large-scale culture of hUCB-MSCs. METHODS: hUCB-MSCs were maintained under hypoxic conditions (3% O2) with 1.8 mM Ca2+ during long-term culture, and their proliferation was evaluated. To characterize the underlying mechanisms, the effects on hypoxia-inducible factor (HIF)-1α and the extracellular signal-regulated kinase (ERK) signaling pathways were investigated. The therapeutic effects in a mouse emphysema model were analyzed and compared with those of naive MSCs. RESULTS: The proliferation of Ca2+/hypoxia-treated hUCB-MSCs was increased compared with that observed using either calcium or hypoxia culture alone, without loss of stem cell marker expression or differentiation ability. The enhancement of the proliferation capacity of hUCB-MSCs by the synergistic effects of Ca2+ and hypoxia was dependent on the expression of HIF-1α and the ERK signaling pathway. The proliferation of Ca2+/hypoxia-treated hUCB-MSCs resulted in a delayed senescence phenotype and increased the expression levels of stemness genes such as Oct4 and Nanog compared to those observed in conventional culture conditions. In addition, Ca2+/hypoxia-treated MSCs transplantation in the mouse emphysema model showed the same therapeutic effects as observed with naive MSCs. CONCLUSIONS: These findings suggest that a Ca2+/hypoxia-based expansion system has applications for the large-scale production of MSCs for therapeutic purposes.
RESUMO
Microfluidics forms the basis of unique experimental approaches that visualize the development of neural structure using micro-scale devices and aids the guidance of neurite growth in an axonal isolation compartment. We utilized microfluidics technology to monitor the differentiation and migration of neural cells derived from human embryonic stems cells (hESC). We cocultured hESC with PA6 stromal cells and isolated neural rosette-like structures, which subsequently formed neurospheres in a suspension culture. We found that Tuj1-positive neural cells but not nestin-positive neural precursor cells (NPC) were able to enter the microfluidics grooves (microchannels), suggesting a neural cell-migratory capacity that was dependent on neuronal differentiation. We also showed that bundles of axons formed and extended into the microchannels.Taken together, these results demonstrated that microfluidics technology can provide useful tools to study neurite outgrowth and axon guidance of neural cells, which are derived from human embryonic stem cells.
