Mesenchymal stem cells for treatment of aortic aneurysms

An aortic aneurysm(AA) is a silent but life-threatening disease that involves rupture. It occurs mainly in aging and severe atherosclerotic damage of the aortic wall. Even though surgical intervention is effective to prevent rupture, surgery for the thoracic and thoraco-abdom-inal aorta is an invasive procedure with high mortality and morbidity. Therefore, an alternative strategy for treatment of AA is required. Recently, the molecular pathology of AA has been clarified. AA is caused by an imbalance between the synthesis and degradation of extracellular matrices in the aortic wall. Chronic inflam-mation enhances the degradation of matrices directly and indirectly, making control of the chronic inflamma-tion crucial for aneurysmal development. Meanwhile, mesenchymal stem cells(MSCs) are known to be ob-tained from an adult population and to differentiate into various types of cells. In addition, MSCs have not only the potential anti-inflammatory and immunosuppres-sive properties but also can be recruited into damagedtissue. MSCs have been widely used as a source for celltherapy to treat various diseases involving graft-versus-host disease, stroke, myocardial infarction, and chronicinflammatory disease such as Crohn's disease clinically.Therefore, administration of MSCs might be availableto treat AA using anti-inflammatory and immnosup-pressive properties. This review provides a summary ofseveral studies on "Cell Therapy for Aortic Aneurysm"including our recent data, and we also discuss the pos-sibility of this kind of treatment.     

The significant effect of the carbohydrate structures on the DNA photocleavage of the quinoxaline-carbohydrate hybrids

The novel DNA interactive quinoxaline-carbohydrate hybrids possessing disaccharides as the carbohydrate moieties were designed and synthesized, and their DNA photocleaving abilities were evaluated in order to examine the effect of the disaccharide structures. The configurations of the glycosidic bonds in the disaccharide strongly affected the DNA photocleaving ability, and two beta-glycosidic bond linkages were very effective for the DNA photocleavage. Furthermore, the quinoxaline-disaccharide hybrids exhibited selective cytotoxicity against cancer cells with photoirradiation.     

Amino acid substitutions in the VanS sensor of the VanA-type vancomycin-resistant Enterococcus strains result in high-level vancomycin resistance and low-level teicoplanin resistance

The vancomycin-resistant enterococci GV1, GV2 and GV3, which were isolated from droppings from broiler farms in Japan have been characterized as VanA-type VRE, which express high-level vancomycin resistance (256 or 512 microg ml(-1), MIC) and low-level teicoplanin resistance (1 or 2 microg ml(-1), MIC). The vancomycin resistances were encoded on plasmids. The vancomycin resistance conjugative plasmid pMG2 was isolated from the GV2 strain. The VanA determinant of pMG2 showed the same genetic organization as that of the VanA genes encoded on the representative transposon Tn1546, which comprises vanRSHAXYZ. The nucleotide sequences of all the genes, except the gene related to the vanS gene on Tn1546, were completely identical to the genes encoded on Tn1546. Three amino acid substitutions in the N-terminal region of the deduced VanS were detected in the nucleotide sequence of vanS encoded on pMG2. There were also three amino acid substitutions in the vanS gene of the GV1 and GV3 strains in the same positions as in the vanS gene of pMG2. Vancomycin induced the increased teicoplanin resistance in these strains.     

Evolution of the maturation rate collapses competitive coexistence

Most theoretical studies on character displacement and the coexistence of competing species have focused attention on the evolution of competitive traits driven by inter-specific competition. We investigated the evolution of the maturation rate which is not directly related to competition and trades off with the birth rate and how it influences competitive outcomes. Evolution may result in the superior competitor becoming extinct if, initially, the inferior competitor has a lower, and the superior one a higher, maturation rate at the coexistence equilibrium. This counterintuitive result is explained by an explosive increase in the adult population of the inferior competitor as a result of the more rapid evolution of its maturation rate, which is caused by differences in the intensity and direction of selection on the maturation rates of the two species and in their adult densities, which are related to differences in their life histories. Thus, a life history trait trade-off with a competitive trait may cause a competitive ecological coexistence to collapse.     

Hyperosmotic stress up-regulates the expression of major vault protein in SW620 human colon cancer cells

The major vault protein (MVP) is the major constituent of the vault particle, the largest ribonuclear protein complex described to date and is identical to lung resistance-related protein (LRP). Although MVP is also expressed in several normal tissues, little is known about its physiological role. MVP played a protective role against some xenobiotics and other stresses. We thus investigated the effect of osmotic stress on MVP expression by treating human colon cancer SW620 cells with sucrose or NaCl. The expression level of both MVP protein and MVP mRNA was increased by the osmostress. Sucrose or sodium chloride could also enhance MVP promoter activity. Inhibition of p38 MAPK in SW620 cells by SB203580 inhibited the expression of MVP under hyperosmotic stress. These findings suggested that osmotic stress up-regulated the MVP expression through p38 MAPK pathway. Down-regulation of MVP expression by MVP interfering RNA (RNAi) in SW620 cells increased the sensitivity of the cells to hyperosmotic stress and enhanced apoptosis. Furthermore, MVP RNAi prevented the osmotic stress-induced, time-dependent increase in phosphorylated Akt. These findings suggest that the PI3K/Akt pathway might be implicated in the cytoprotective effect of MVP.Our data demonstrate that exposure of cells to hyperosmotic stress induces MVP that might play an important role in the protection of the cells from the adverse effects of osmotic stress.     

Putative "stemness" gene jam-B is not required for maintenance of stem cell state in embryonic, neural, or hematopoietic stem cells

Many genes have been identified that are specifically expressed in multiple types of stem cells in their undifferentiated state. It is generally assumed that at least some of these putative "stemness" genes are involved in maintaining properties that are common to all stem cells. We compared gene expression profiles between undifferentiated and differentiated embryonic stem cells (ESCs) using DNA microarrays. We identified several genes with much greater signal in undifferentiated ESCs than in their differentiated derivatives, among them the putative stemness gene encoding junctional adhesion molecule B (Jam-B gene). However, in spite of the specific expression in undifferentiated ESCs, Jam-B mutant ESCs had normal morphology and pluripotency. Furthermore, Jam-B homozygous mutant mice are fertile and have no overt developmental defects. Moreover, we found that neural and hematopoietic stem cells recovered from Jam-B mutant mice are not impaired in their ability to self-renew and differentiate. These results demonstrate that Jam-B is dispensable for normal mouse development and stem cell identity in embryonic, neural, and hematopoietic stem cells.     

Development of a glutathione production process from proteinaceous biomass resources using protease-displaying <Emphasis Type="Italic">Saccharomyces cerevisiae</Emphasis>

Glutathione is a valuable tri-peptide that is widely used in the pharmaceutical, food, and cosmetic industries. Glutathione is produced industrially by fermentation using Saccharomyces cerevisiae, and supplementation of fermentation with several amino acids can increase intracellular GSH content. More recently, however, focus has been given to protein as a resource for biofuel and fine chemical production. We demonstrate that expression of a protease on the cell surface of S. cerevisiae enables the direct use of keratin and soy protein as a source of amino acids and that these substrates enhanced intracellular GSH content. Furthermore, fermentation using soy protein also enhanced cell concentration. GSH fermentation from keratin and to a greater extent from soy protein using protease-displaying yeast yielded greater GSH productivity compared to GSH fermentation with amino acid supplementation. This protease-displaying yeast is potentially applicable to a variety of processes for the bio-production of value-added chemicals from proteinaceous biomass resources.