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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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Genetic relationships among 15 South West European populations of Polyommatus coridon were evaluated by the electrophoretic study of 16 gene-enzyme systems. Nei's indexes I and D and other statistics demonstrated that two different species are involved, identifiable as Polyommatus coridon (six populations from Southern France and Italy) and Polyommatus caelestissimus (nine populations from Spain), respectively. The Spanish complex is characterized by a different genetic balance, involving much higher degree of interdemic differentiation. It also differs from populations from France and Italy on one alternative locus showing complete fixation. Species-level distinction is independent of haploid chromosome numbers that vary from 87 to 88 in both groups. An evaluation of selective pressures as operated by climatic factors was attempted. The Pleistocene radiation of this group and consequent patterns of the gene flow were reconstructed using spatial autocorrelation analysis.  相似文献   
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Cytochemical observations indicate the occurrence of leucoanthocyanidinsin the protein bodies of Cercis siliquastrum endosperm; theendosperm cell walls give a positive Mayer's test, indicatingmucopolysac-charides. These results are discussed in relationto the endosperm-imposed dormancy of the seed. Cercis siliquastrum, endosperm-imposed dormancy, leucoanthocyanidins, mucopolysac-charides  相似文献   
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ABSTRACT. Among secondary metabolites, the acetylated hemiacetal sesquiterpene euplotin C has been isolated from the marine, ciliated protist Euplotes crassus, and provides an effective mechanism for reducing populations of potential competitors through its cytotoxic properties. However, intracellular signaling mechanisms and their functional correlates mediating the ecological role of euplotin C are largely unknown. We report here that, in E. vannus (an Euplotes morphospecies that does not produce euplotin C and shares with E. crasssus the same interstitial habitat), euplotin C rapidly increases the intracellular concentration of both Ca2+ and Na+, suggesting a generalized effect of this metabolite on cation transport systems. In addition, euplotin C does not induce oxidative stress, but modulates the electrical properties of E. vannus through an increase of the amplitude of graded action potentials. These events parallel the disassembling of the ciliary structures, the inhibition of cell motility, the occurrence of aberrant cytoplasmic vacuoles, and the rapid inhibition of phagocytic activity. Euplotin C also increases lysosomal pH and decreases lysosomal membrane stability of E. vannus. These results suggest that euplotin C exerts a marked disruption of those homeostatic mechanisms whose efficiency represents the essential prerequisite to face the challenges of the interstitial environment.  相似文献   
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