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Background aims

Multipotent mesenchymal stromal cell (MSC)-based medicines are extensively investigated for use in regenerative medicine and immunotherapy applications. The International Society for Cell and Gene Therapy (ISCT) proposed a panel of cell surface molecules for MSC identification that includes human leukocyte antigen (HLA)-DR as a negative marker. However, its expression is largely unpredictable despite production under tightly controlled conditions and compliance with current Good Manufacturing Practices. Herein, we report the frequency of HLA-DR expression in 81 batches of clinical grade bone marrow (BM)-derived MSCs and investigated its impact on cell attributes and culture environment.

Methods

The levels of 15 cytokines (interleukin [IL]-1β, IL-4, IL-6, IL-10, IL-17A, IL-17F, IL-21, IL-22, IL-23, IL-25, IL-31, IL-33, interferon-γ, soluble CD40 ligand and tumor necrosis factor-α) were determined in sera supplements and supernatants of BM-MSC cultures. Identity, multipotentiality and immunopotency assays were performed on high (>20% of cells) and low (≤20% of cells) HLA-DR+ cultures.

Results

A correlation was found between HLA-DR expression and levels of IL-17F and IL-33. Expression of HLA-DR did neither affect MSC identity, in vitro tri-lineage differentiation potential (into osteogenic, chondrogenic and adipogenic lineages), nor their ability to inhibit the proliferation of stimulated lymphocytes.

Discussion

Out of 81 batches of BM-MSCs for autologous use analyzed, only three batches would have passed the ISCT criteria (<2%), whereas 60.5% of batches were compliant with low HLA-DR values (≤20%). Although a cause–effect relationship cannot be drawn, we have provided a better understanding of signaling events and cellular responses in expansion culture conditions relating with HLA-DR expression.  相似文献   
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The recent expansion of Pentecostalism and independent churches in Africa has generated growing interest among social scientists. This attention parallels a renewed interest among Africanists on witchcraft and occult activities, also believed by many to be increasing. Some suggest the two trends may be related, but it remains unclear how and why. Drawing on a study of Pentecostalism and health in the city of Chimoio, Mozambique, in 2002–03 that focused on attitudes toward recent social change, we argue that structural adjustment economic reforms have deepened economic inequality and exacerbated household stresses that affect men and women differently. Women increasingly seek spiritual help for reproductive health problems from Pentecostal churches, whereas men disproportionately pay traditional healers to engage "occult" practices to manage misfortune related to employment. The increased resort to both spiritual resources reveals social distress caused by economic adjustment, with important implications for health programs.  相似文献   
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The physiological role of peroxisomal ascorbate peroxidases (pAPX) is unknown; therefore, we utilized pAPX4 knockdown rice and catalase (CAT) inhibition to assess its role in CAT compensation under high photorespiration. pAPX4 knockdown induced co‐suppression in the expression of pAPX3. The rice mutants exhibited metabolic changes such as lower CAT and glycolate oxidase (GO) activities and reduced glyoxylate content; however, APX activity was not altered. CAT inhibition triggered different changes in the expression of CAT, APX and glutathione peroxidase (GPX) isoforms between non‐transformed (NT) and silenced plants. These responses were associated with alterations in APX, GPX and GO activities, suggesting redox homeostasis differences. The glutathione oxidation‐reduction states were modulated differently in mutants, and the ascorbate redox state was greatly affected in both genotypes. The pAPX suffered less oxidative stress and photosystem II (PSII) damage and displayed higher photosynthesis than the NT plants. The improved acclimation exhibited by the pAPX plants was indicated by lower H2O2 accumulation, which was associated with lower GO activity and glyoxylate content. The suppression of both pAPXs and/or its downstream metabolic and molecular effects may trigger favourable antioxidant and compensatory mechanisms to cope with CAT deficiency. This physiological acclimation may involve signalling by peroxisomal H2O2, which minimized the photorespiration.  相似文献   
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Two slow‐growing plant species (Chamaerops humilis, L. and Cycas revoluta Thunb.) were exposed to elevated CO2 conditions over a 20‐month period in order to study the CO2 effect on growth, photosynthetic capacity and leaf carbon (C) management. The ambient isotopic 13C/12C composition (δ13C) of the greenhouse module corresponding to elevated CO2 (800 μmol mol?1 CO2) conditions was changed from δ13C ca. ?12.8±0.3‰ to ca. ?19.2±0.2‰. Exposure of these plants to elevated CO2 enhanced dry mass (DM) by 82% and 152% in Chamerops and Cycas, respectively, mainly as a consequence of increases in plant level photosynthetic rates. However, analyses of ACi curve parameters revealed that elevated CO2 diminished leaf photosynthetic rates of Chamaerops whereas in Cycas, no photosynthetic acclimation was detected. The fact that Chamaerops plants had a lower DM increase, together with a longer leaf C residence time and a diminished capacity to respire recently fixed C, suggests that this species was unable to increase C sink strength. Furthermore, the consequent C source/sink imbalance in Chamaerops might have induced the downregulation of Rubisco. Cycas plants were capable of avoiding photosynthetic downregulation due to a greater ability to increase C sink strength, as was confirmed by DM values, and 12C‐enriched CO2 labeling data. Cycas developed the ability to respire a larger proportion of recently fixed C and to reallocate the recently fixed C away from leaves to other plant tissues. These findings suggest that leaf C management is a key factor in the responsiveness of slow‐growing plants to future CO2 scenarios.  相似文献   
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In the temperate north-western Mediterranean Sea, large-scale disease outbreaks in benthic invertebrate species have recently occurred during climatic anomalies characterized by elevated seawater temperatures. One of the most affected species was the red gorgonian Paramuricea clavata , a key species of highly diverse communities dwelling in dim-lit habitats in the Mediterranean. From diseased P. clavata colonies, we isolated culturable bacteria associated to tissue lesions in order to investigate their potential as pathogens. Inoculation of four bacterial isolates onto healthy P. clavata in aquaria caused disease signs similar to those observed during the 2003 mortality event. The infection process was dependent on elevated seawater temperatures, in a range of values consistent with recordings performed in the field during the climatic anomalies. Among the four isolates, we identified a Vibrio coralliilyticus strain that showed virulence to P. clavata . This strain was re-isolated from diseased colonies during the experimentations. V. coralliilyticus has been previously identified as a thermodependent pathogen of a tropical coral species, emphasizing a causal role of this infectious agent in the P. clavata disease. Taking into consideration predicted global warming over the coming decades, a better understanding of the factors and mechanisms that affect the disease process will be of critical importance in predicting future threats to temperate gorgonians communities in the Mediterranean Sea.  相似文献   
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