RESULTS: Several ascending and descending monotonic key genes were identified by Monotonic Feature Selector. The identified descending monotonic key genes are related to stemness or regulation of cell cycle while ascending monotonic key genes are associated with the functions of mesangial cells. The TFs were arranged in a co-expression network in order of time by Time-Ordered Gene Co-expression Network (TO-GCN) analysis. TO-GCN analysis can classify the differentiation process into three stages: differentiation preparation, differentiation initiation and maturation. Furthermore, it can also explore TF-TF-key genes regulatory relationships in the muscle contraction process.
CONCLUSIONS: A systematic analysis for transcriptomic profiling of MSC differentiation into mesangial cells has been established. Key genes or biomarkers, TFs and pathways involved in differentiation of MSC-mesangial cells have been identified and the related biological implications have been discussed. Finally, we further elucidated for the first time the three main stages of mesangial cell differentiation, and the regulatory relationships between TF-TF-key genes involved in the muscle contraction process. Through this study, we have increased fundamental understanding of the gene transcripts during the differentiation of MSC into mesangial cells.
Methods: Twenty-seven patients with history of anterior myocardial infarction (MI) and baseline left ventricular ejection fraction (LVEF) of less than 35% were recruited into this study. Patients who are eligible for revascularization were grouped into group A (MSCs infusion with concurrent revascularization) or group B (revascularization only) while patients who were not eligible for revascularization were allocated in group C to receive intracoronary MSCs infusion. LV function was measured using echocardiography.
Results: Patients who received MSCs infusion (either with or without revascularization) demonstrated significant LVEF improvements at 3, 6 and 12 months post-infusion when compared to baseline LVEF within its own group. When comparing the groups, the magnitude of change in LVEF from baseline for third visits i.e., 12 months post-infusion was significant for patients who received MSCs infusion plus concurrent revascularization in comparison to patients who only had the revascularization procedure.
Conclusions: MSCs infusion significantly improves LV function in ICM patients. MSCs infusion plus concurrent revascularization procedure worked synergistically to improve cardiac function in patients with severe ICM.
METHODS: In this study, CD24 population from the MCF-7 spheroid was sorted and subjected to spheroid formation test, stem cell markers immunofluorescence, invasion and migration test as well as microRNA expression profiling.
RESULTS: Sorted MCF-7 CD24 cells from primary spheroids were able to reform its 3D spheroid shape after 7 days in non-adherent culture conditions. In contrast to the primary spheroids, the expression of SOX-2, CD44, CD49f and Nanog were dim in MCF-7 CD24+ cells. Remarkably, MCF-7 CD24 cells were found to show high expression of ALDH1 protein which may have resulted in these cells exhibiting higher resistance against doxorubicin and cisplatin when compared to that of the parental cells. Moreover, microRNA profiling has shown that the absence of cancer stem cell properties were consistent with the downregulation of major cancer stem cells related pathways including Hedgehog, Wnt and MAPK signalling pathways. However, the upregulated pathways such as adherans junctions, focal adhesion and tight junction suggest that CD24+ cells were probably at an epithelial-like state of cell transition.
CONCLUSION: In conclusion, neglected CD24+ cells in MCF-7 spheroid did not exhibit typical breast CSCs properties. The presence of miRNAs and their analysed pathways suggested that these cells could be a distinct intermediate cell state in breast CSCs.
METHODS: OR cells were established via stepwise-dose escalation and limiting single-cell dilution method. We then evaluated Osimertinib resistance potential via cell viability assay. Proteins expression related to EGFR-signalling, epithelial to mesenchymal transition (EMT), and autophagy were analyzed via western blot.
RESULTS: OR cell lines exhibited increased drug resistance potential compared to H1975. Distinguishable mesenchymal-like features were observed in OR cells. Protein expression analysis revealed EGFR-independent signaling involved in the derived OR cells as well as EMT and autophagy activity.
CONCLUSION: We generated OR cell lines in-vitro as evidenced by increased drug resistance potential, increased mesenchymal features, and enhanced autophagy activity. Development of Osimertinib resistance cells may serve as in-vitro model facilitating discovery of molecular aberration present during acquired mechanism of resistance.
METHODS: hUC-MSCs were labelled with GFP-Luc2 protein, followed by characterisation with flow cytometry. Upon intravenous infusion of transduced hUC-MSCs into the healthy BALB/c mice, the cells were dynamically monitored through the bioluminescent imaging (BLI) approach.
RESULTS: Transduction of hUC-MSCs with GFP-Luc2 not only preserved the characteristics of MSCs, but also allowed live monitoring of transduced cells in the mice model. Upon systemic administration, BLI showed that transduced hUC-MSCs first localised predominantly in the lungs of healthy BALB/c mice and mainly remained in the lungs for up to 3 days before eventually cleared from the body. At terminal sacrifice, plasma chemistry biomarkers remained unchanged except for C-peptide levels, which were significantly reduced in the hUC-MSCs group. Histopathological findings further revealed that hUC-MSCs infusion did not cause any adverse effects and toxicity to lung, liver and heart tissues.
CONCLUSIONS: Collectively, systemically administrated hUC-MSCs was safe and demonstrated dynamic homing capacity before eventually disappearing from the body.