Stem cells from fetal tissue protect against aging and possess greater proliferative capacity than their adult counterparts. These cells can more readily expand in vitro and senesce later in culture. However, the underlying molecular mechanisms for these differences are still not fully understood. In this study, we used a robust rank aggregation (RRA) method to discover robust differentially expressed genes (DEGs) between fetal bone marrow mesenchymal stem cells (fMSCs) and aged adult bone marrow mesenchymal stem cells (aMSCs). Multiple methods, including gene set enrichment analysis (GSEA), Gene Ontology (GO) analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed for functional annotation of the robust DEGs, and the results were visualized using the R software. The hub genes and other genes with which they interacted directly were detected by protein–protein interaction (PPI) network analysis. Correlation of gene expression was measured by Pearson correlation coefficient. A total of 388 up-regulated and 289 down-regulated DEGs were identified between aMSCs and fMSCs. We found that the down-regulated genes were mainly involved in the cell cycle, telomerase activity, and stem cell proliferation. The up-regulated DEGs were associated with cell adhesion molecules, extracellular matrix (ECM)–receptor interactions, and the immune response. We screened out four hub genes, MYC, KIF20A, HLA-DRA, and HLA-DPA1, through PPI-network analysis. The MYC gene was negatively correlated with TXNIP, an age-related gene, and KIF20A was extensively involved in the cell cycle. The results suggested that MSCs derived from the bone marrow of an elderly donor present a pro-inflammatory phenotype compared with that of fMSCs, and the HLA-DRA and HLA-DPA1 genes are related to the immune response. These findings provide new insights into the differences between aMSCs and fMSCs and may suggest novel strategies for ex vivo expansion and application of adult MSCs.
Objectives To investigate the effect of simvastatin intervention on the changes of blood pressure, serum lipid fluctuation and aortic configuration induced by high sodium plus high fat diets in rats. Methods Sixty adult male SD rats were randomly divided into five groups (n=12); control group (N), high salt group (S), high fat group (F), high salt+high fat group (SF) and high salt plus high fat +simvastatin group (T). After fed for 16 weeks, the rats were subject to determine blood pressures and serum concentrations of TC, TG and sCD40L. The expression of CD40/CD40L in the root of ascending aorta was detected by immunohistochemical method. The thickness of intima media in the ascending aorta as well as the ratio of lumen area/total vascular area were measured and calculated after HE staining. Results In S group, F group and SF group, systolic blood pressure was significantly higher than that in N group ( p<0.01). systolic blood pressure in T group were slightly higher than that in N group with statistical significance and significantly slower than that in SF group. The serum concentrations of triglycerides (TG) and total cholesterol (TC) in F group and SF group were significantly higher than those in N group and T group ( p<0.01), and no significant difference between S group, N group and T group was observed. In S group, F group and SF group, the serum concentrations of sCD40L were higher than that in N group and T group ( p<0.05), meanwhile that in SF group was also higher than that in S group and F group ( p<0.05). However, no significant difference of sCD40L concentration between S group and F group as well as N group and T group was observed. The expression of CD40/CD40L in the ascending aorta in S group, F group and SF group was higher than that in N group and T group ( p<0.05), and that in SF group was higher than in S group and F group ( p<0.05), and no significantly difference of CD40/CD40L expression between S group and F group as well as N group and T group was observed. The thickness of intima media in S group, F group, SF group was significantly thicker than that in N group ( p<0.01), and no significantly difference of intima media thickness between T group and N group was observed. The ratio of lumen area/total vascular area in S group, F group and SF group was smaller than that in N group ( p<0.05), and no significant difference of ratio between T group and N group was found. Conclusions Feeding high fat plus high salt leads to blood pressure elevation, induces atherosclerosis, increases serum concentrations of sCD40L and enhances the expression of CD40/CD40L in arterial tissues. The combination of stimulus has stronger effect than a single factor. Statins protect the arterial tissues against atherosclerosis by decreasing the level of serum sCD40L and inhibiting the expression of arterial tissues CD40/CD40L.Heart 2012;98(Suppl 2): E1-E319 E55 ABSTRACTS on 8 May 2018 by guest. Protected by copyright.
Lyophilized platelet-rich fibrin (L-PRF) was shown to further activate resident platelets in platelet-rich fibrin causing a higher amount of growth factors release. However, it still required further experimental studies to resolve the uncontrolled degradation and burst release problem. In this study, the nature crosslinker genipin is introduced to improve the performance of L-PRF scaffold. We used a series of gradient concentration genipin solutions to react with L-PRF. The crosslinking degree, micro morphology, mean pore size, water absorption and mechanical properties of the crosslinked scaffold were evaluated. In order to study the effect of genipin modification on the release kinetics of growth factors from L-PRF, we detected the release of platelet-derived growth factor, vascular endothelial growth factor and transforming growth factor in vitro by ELISA. To investigate the biodegradability of the crosslinked L-PRF in vivo, the scaffolds were transplanted subcutaneously into backs of rats, and the materials were recovered at 1, 2 and 4 weeks after implantation. The biodegradation, inflammatory reaction and biocompatibility of the scaffolds were examined by histological staining. Finally, the genipin crosslinked/uncrosslinked L- Platelet-rich fibrin scaffolds were implanted with freshly prepared SHED cell sheets into rat critical size calvarial defects and the skull samples were recovered to examine the treatment efficacy of genipin crosslinked L-PRF by histologic and radiographic approaches. Results of this study indicated that genipin can be used to modify L-PRF at room temperature at a very low concentration. Genipin-modified L-PRF shows better biomechanical performance, slower biodegradation, good bioavailable and sustained release of growth factors. The 0.01% w/v and 0.1% w/v genipin crosslinked L-PRF have good porous structure and significantly promote cell proliferation and enhance the expression of key genes in osteogenesis in vitro, and work best in promoting bone regeneration in vivo.
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