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Background

Mesenchymal stromal cells (MSCs) are a promising candidate for treatment of inflammatory disorders, but their efficacy in human inflammatory bowel diseases (IBDs) has been inconsistent. Comparing the results from various pre-clinical and clinical IBD studies is also challenging due to a large variation in study designs.

Methods

In this comparative pre-clinical study, we compared two administration routes and investigated the safety and feasibility of both fresh and cryopreserved platelet-lysate–expanded human bone marrow–derived MSCs without additional licensing in a dextran sodium sulfate (DSS) colitis mouse model both in the acute and regenerative phases of colitis. Body weight, macroscopic score for inflammation and colonic interleukin (IL)-1β and tumor necrosis factor (TNF)α concentrations were determined in both phases of colitis. Additionally, histopathology was assessed and Il-1β and Agtr1a messenger RNA (mRNA) levels and angiotensin-converting enzyme (ACE) protein levels were measured in the colon in the regenerative phase of colitis.

Results

Intravenously administered MSCs exhibited modest anti-inflammatory capacity in the acute phase of colitis by reducing IL-1β protein levels in the inflamed colon. There were no clear improvements in mice treated with fresh or cryopreserved unlicensed MSCs according to weight monitoring results, histopathology and macroscopic score results. Pro-inflammatory ACE protein expression and shedding were reduced by cryopreserved MSCs in the colon.

Conclusions

In conclusion, we observed a good safety profile for bone marrow–derived platelet lysate–expanded MSCs in a mouse pre-clinical colitis model, but the therapeutic effect of MSCs prepared without additional licensing (i.e. such as MSCs are administered in graft-versus-host disease) was modest in the chosen in vivo model system and limited to biochemical improvements in cytokines without a clear benefit in histopathology or body weight development.  相似文献   
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BACKGROUND: The technique of coronary stenting has evolved over recent years, with improved stent technology and effective antiplatelet therapies to prevent stent thrombosis. In Europe, reductions in stent and equipment costs have resulted from increased market competition. The impact of these changes on the in-hospital procedural cost of percutaneous coronary intervention (PCI) in the current clinical setting is not known. METHODS: We compared the initial equipment and pharmaceutical costs of one hundred consecutive, unselected patients undergoing PCI in 1998 to a similar population who underwent PCI in 1994. RESULTS: Similar patient characteristics were noted, yet more complex disease (multivessel, AHA type B2/C lesions) was treated in the 1998 population. The stent utilization rate (83% vs 15%, p < 0.0001) and use of intravenous and/or oral antiplatelet therapy (abciximab, ticlopidine) (64% vs 4%, p < 0.0001) was higher in 1998. Similar angiographic success was achieved in each group with low complication rates. Mean hospital stay was reduced in the 1998 group (2.6 +/- 2.8 vs 4.3 +/- 3.8 days, p < 0.001). Repeat PCI was required more frequently in the 1994 population (26% vs 9%, p < 0.001). Overall there was no significant difference in the mean equipment cost between the two groups ( pound 1551 vs pound 1422, p=ns). CONCLUSION: Despite the widespread use of coronary stenting and antiplatelet therapies there appears to be no difference in current in-hospital equipment costs for PCI compared to 1994. Improved clinical outcomes in the 1998 population imply that stenting is a cost-effective therapy.  相似文献   
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Here we compare human monoclonal antibody (MAb) production from mouse strains that carry disruptions of their endogenous mouse IgH/IgK loci and harbor human IgM + Igkappa(BABkappa) or human IgM + Igkappa + IgA transloci (BABkappa,lambda). We found that whereas both strains proved effective for the isolation of antigen-specific IgM antibodies, many of the IgM MAbs elicited from BABkappa comprise human mu chains that are associated with mouse lambda chains. In contrast, BABkappa,lambda mice gave rise to fully functional, polymeric human IgM antibodies comprising both human IgH and human IgL chains. Therefore, the inclusion of a human Iglambda translocus (in addition to the human IgH + Igkappa transloci) not only diminishes problems of endogenous mouse Iglambda expression but also provides a strain of mice that yields fully human MAbs to a wide range of antigens, as witnessed by the isolation of MAbs to human blood cells, tumor cell lines, and an immunoglobulin idiotype.  相似文献   
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A growth chamber experiment was carried out to investigate the influence of day length and temperature on the development of flowering in eight varieties of the three grain lupin species Lupinus albus (Wat and C3396), L. angustifolius (Gungurru, Polonez and W26) and L. luteus, (Juno, Radames and Teo). The plants were grown at two temperatures, 10°C and 18°C, in combination with five daylength regimes: 10, 14, 18, 24 h day at full light intensity and 10 h full light extended with 8 h low intensity light. Increased daylength decreased days from sowing to flowering in all varieties, but had little effect on thermal time to flowering in most varieties. However, C3396, W26 and Radames had a significantly longer thermal time to flowering at high, non‐vernalising temperature (18°C) at short daylengths. Low light intensity daylength extension did not significantly influence thermal time to flowering. For flower initiation, measured as number of leaves on the main stem three types of response were found. All varieties formed fewer leaves on the main stem at 10°C than at 18°C, although the two thermo‐neutral varieties of L. luteus, Juno and Teo, gave only a small response to temperature and daylength. In Polonez, Gungurru and Wat, low temperature decreased leaf number, but there was only a small response to changes in daylength. Three varieties, C3396, W26 and Radames, showed longer thermal time to flowering at 18°C with short daylengths. This could be explained by a greater number of main stem leaves formed at short daylength at non‐vernalising temperatures. Increased daylength decreased leaf number in these varieties, but never to a smaller number than for plants grown at 10°C. In these varieties, low intensity extension of the daylength had a similar (W26, Radames) or decreased (C3396) effect compared to full light extension. The hastening of time to flowering by long days could be separated into two effects: a high light energy effect hastened development by increasing the rate of leaf appearance in all varieties, while low light energy in thermo‐sensitive varieties was able to substitute for vernalisation by decreasing leaf number.  相似文献   
69.
Microsatellites were identified by screening 2294 GenBank entries available for Atlantic cod (Gadus morhua L.), mainly representing expressed sequence tags and cDNA sequences. Ninety‐two novel microsatellite loci (tetra‐, tri‐ and dinucleotides) were characterized on 96 individuals. This strategy yielded 25 gene‐associated polymorphic microsatellite markers (11 tri‐ and 14 dinucleotides) with two to 20 alleles and an average heterozygosity of 0.48 in the population studied (range 0.02–0.89). One marker exhibited significant homozygote excess, and one of the primer pairs amplified two linked markers. The gene identity was determined at nine of the loci, confirming the associated microsatellites as type I markers.  相似文献   
70.

Background  

S. meliloti forms indeterminate nodules on the roots of its host plant alfalfa (Medicago sativa). Bacteroids of indeterminate nodules are terminally differentiated and, unlike their non-terminally differentiated counterparts in determinate nodules, do not accumulate large quantities of Poly-3-hydroxybutyrate (PHB) during symbiosis. PhaZ is in intracellular PHB depolymerase; it represents the first enzyme in the degradative arm of the PHB cycle in S. meliloti and is the only enzyme in this half of the PHB cycle that remains uncharacterized.  相似文献   
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