Project description:MiRNA microarray analysis was performed on exosomes secreted by mouse MSC cells under two different conditions of normal oxygen and hypoxia, in order to find out the different miRNAs in exosomes secreted by MSC under two different conditions.
Project description:Transcriptional profiling of human mesenchymal stem cells comparing normoxic MSCs cells with hypoxic MSCs cells. Hypoxia may inhibit senescence of MSCs during expansion. Goal was to determine the effects of hypoxia on global MSCs gene expression. Two-condition experiment, Normoxic MSCs vs. Hypoxic MSCs.
Project description:Transcriptional profiling of human mesenchymal stem cells comparing normoxic MSCs cells with hypoxic MSCs cells. Hypoxia may inhibit senescence of MSCs during expansion. Goal was to determine the effects of hypoxia on global MSCs gene expression.
Project description:Human umbilical cord matrix-derived mesenchymal stromal cells (UCM-MSC) are advantageous since can be easily obtained and display special interest as universal and feasible add-on therapy for myocardial infarction (MI). In this study, UCM-MSC from two umbilical cords, UC-A and UC-B, were transplanted in a murine MI model to investigate consistency and durability of the therapeutic benefits. Both cellular products supported sustained and long-term beneficial therapeutic effect. In vitro, the two cell products displayed similar ability to induce the formation of vessel-like structures and comparable transcriptome in normoxia and hypoxia, apart from expression differences in a small subset of genes associated with MHC Class I. These findings support that UCM-MSC are strong candidates to assist the treatment of MI whilst calling for the discussion on methodologies to characterize and select best performing UCM-MSC before clinical application.
Project description:The innate repair and regeneration potential of skeletal tissues such as the intervertebral disc and articular cartilage is extremely limited, in part due to their avascularity and low cell density. Despite recent advances in MSC-based disc and cartilage regeneration, key challenges remain, including the sensitivity of these cells to in vivo microenvironmental stress such as low oxygen and nutrient levels. The objective of this study was to investigate whether preconditioning with hypoxia and/or transforming growth factor-beta (TGF-β) can enhance MSC survival and extracellular matrix production in a low oxygen and nutrient-limited microenvironment. Secondarily, the effects of donor variability on the response of MSCs to preconditioning was examined. MSCs from multiple bovine donors were preconditioned in monolayer in normoxia or hypoxia, with or without TGF-β. The effects of preconditioning on MSC gene expression during monolayer expansion were examined using microarrays.
Project description:Lysates of Mycobacterium tuberculosis (H37Rv auxotroph mc(2)6020) grown under various conditions (normoxia, hypoxia, reactivation from hypoxia) probed the serine hydrolase probe with ActivX-desthiobiotin FP.
Project description:Altered bone marrow hematopoiesis and immune suppression is a hallmark of myelodysplastic syndrome (MDS). While the bone marrow microenvironment influences malignant hematopoiesis, the mechanism leading to MDS-associated immune suppression is unknown. We tested whether mesenchymal stromal cells (MSCs) contribute to this process. Here, we developed a model to study cultured MSCs from MDS patients compared to similar aged matched normal controls for regulation of immune function. MSCs from MDS patients (MDS-MSC) and healthy donor MSC (HD-MSC) exhibited a similar in vitro phenotype and neither had a direct effect on NK cell function. However, when MDS and HD-MSCs were cultured with monocytes, only the MDS-MSCs acquired phenotypic and metabolic properties of myeloid-derived suppressor cells (MDSCs), with resulting suppression of NK cell function, along with T cell proliferation. A unique MSC transcriptome was observed in MDS-MSCs compared to HD-MSCs, including increased expression of the reactive oxygen species (ROS) regulator, ENC1. High ENC1 expression in MDS-MSC induced suppressive monocytes with increased INHBA, a gene that encodes for a member of the TGF? superfamily of proteins. These monocytes also had reduced expression of the TGF? transcriptional repressor MAB21L2, further adding to their immune suppressive function. Silencing ENC1 or inhibiting ROS production in MDS-MSCs abrogated the suppressive function of MDS-MSC conditioned monocytes. In addition, silencing MAB21L2 in healthy MSC conditioned monocytes mimicked the MDS-MSC suppressive transformation of monocytes. Our data demonstrate that MDS-MSCs are responsible for inducing an immune suppressive microenvironment in MDS through an indirect mechanism involving monocytes.