Project description:The primary objective of this prospective observational study is to characterize the gut and oral microbiome as well as the whole blood transcriptome in gastrointestinal cancer patients and correlate these findings with cancer type, treatment efficacy and toxicity. Participants will be recruited from existing clinical sites only, no additional clinical sites are needed.
Project description:We selected three neonicotinoids and nicotine to expose the hBMSCs We obtained the gene expression which can help us identify the potential toxic effects of NEOs on human body
Project description:We conducted a detailed time-course RNA expression profiling during the early trans-differentiation of human bone marrow-derived MSCs (hBMSCs).
Project description:In this study, we performed the high-throughput sequencing of hBMSCs between day 0 and day 21 during induction of osteogenic differentiation, followed by analysis of the different expression in whole transcriptomes.
Project description:Parkinson’s disease (PD) is characterized by a selective loss of dopamine (DA) neurons in the human midbrain causing motor dysfunctions. The exact mechanism behind dopaminergic cell death is still not completely understood and, so far, no cure or neuroprotective treatment for PD is available. Recent studies have brought attention to the wide array of bioactive molecules produced by mesenchymal stem cells (MSCs), generally referred to as the secretome. Herein, we evaluated whether human MSCs-bone marrow derived (hBMSCs) secretome would be beneficial in a PD pre-clinical model, when compared directly with cell transplantation of hBMSCs alone. We used a 6-hydroxydpomanie (6-OHDA) rat PD model, and motor behavior was evaluated at different time points after treatments (1, 4 and 7 weeks). The impact of the treatments in the recovery of DA neurons was estimated by determining TH-positive neuronal densities in the substantia nigra and fibers in the striatum, respectively, at the end of the behavioral characterization. Furthermore, we determined the effect of the hBMSCs secretome on the neuronal survival of human neural progenitors in vitro, and characterized the secretome through proteomic-based approaches. This work demonstrates that the injection of hBMSCs secretome potentiated the histological recovery of DA neurons, when compared to transplantation of hBMSCs themselves, a fact that probably explains the improved behavioral performance of secretome-injected animals in the staircase test. Moreover, we observed that hBMSCs secretome induces higher levels of in vitro neuronal differentiation. Finally, the proteomic analysis revealed that hBMSCs secrete a variety of important exosome-related molecules such as those related with the ubiquitin-proteasome and histone systems. Overall, this work provided important insights on the potential use of hBMSCs secretome as a therapeutic tool for PD, and further confirms the importance of the secreted molecules rather than the transplantation of hBMSCs for the observed positive effects. These could be likely through normalization of defective processes in PD, namely proteostasis or altered gene transcription, which lately can lead to neuroprotective effects.
Project description:In this experiment human Bone Marrow Stem Cells (hBMSCs) are grown in co-culture with Human Umbilical Vein Endothelial Cells (HUVECs) for 5 days, HUVECs are removed by trypsination before call harvest. In parallel hBMSCs are grown in monoculture as a control for 5 days, and a sham trypsination performed before harvesting of the cells. The aim for the project is to analyze the gene expression alteration in hBMSCs resulting from BMSCs being co-cultured with HUVECs.
Project description:Microarray analysis was used to evaluate expression differences from a single donor human bone marrow stromal cells (hBMSCs) as a function of varied polymer-based tissue engineering scaffolds. The results revealed that gene expression patterns of hBMSCs grouped according to scaffold.
Project description:We conducted a detailed time-course RNA expression profiling during the early trans-differentiation of human bone marrow-derived MSCs (hBMSCs).
Project description:Molecular understanding of osteogenic differentiation (OD) of human bone-marrow derived mesenchymal stem cells (hBMSCs) is important for regenerative medicine and has direct implications to cancer. Here we report that the RNF4 ubiquitin ligase is essential for OD of hBMSCs, and that RNF4 deficient hBMSCs fail to differentiate and remain as stalled progenitors. Remarkably, addition of media from differentiating hBMSCs to RNF4-deficient MSCs alleviated the block in OD. Transcriptional analysis of RNF4-dependent gene signature identified two secreted factors; BMP6 and the guidance molecule BMP6 co-receptor RGMb (Dragon). Knockdown of either RGMb or BMP6 in hBMSCs inhibit differentiation, and only the combined addition of purified RGMb and BMP6 proteins to RNF4-deficient MSCs fully restored osteogenic differentiation. Moreover, RNF4-RGMb axis is highly relevant cancer cell survival and tumorigenicity, including osteosarcoma and Therapy-resistant melanoma cells. In accordance, in human melanoma biopsies high level of RGMb correlates with high level of RNF4, and is associated with resistance to molecular therapy and poor prognosis of patients. Thus, RNF4~BMP6~RGMb is a molecular axis that is key for OD and tumorigenesis.
