Project description:Chronic inflammation leading to pro-inflammatory macrophage infiltration contributes to the pathogenesis of type 2 diabetes and subsequently the development of diabetic nephropathy. Mesenchymal stem cells (MSCs) possess unique immunomodulatory and cytoprotective properties making them an ideal candidate for therapeutic intervention We used microarrays to detail changes in the gene expression profile of monocytes isolated from type 2 diabetic patients with end-stage renal disease and non-diabetic control subjects following co-culture with MSCs. Control blood samples were obtained from 4 donors from the Australian Red Cross Blood Service. Blood was also obtained from 5 diabetic patients with end-stage renal disease receiving haemodialysis at the Monash Medial Centre. CD14+ monocytes were isolated from blood using microbeads and co-cultured for 48 hours with and without human bone marrow-derived MSCs using an in vitro transwell system. An Affymetrix GeneChip Human Gene 2.0 ST array was used.
Project description:Microarray analysis of bone marrow multipotent mesenchymal stromal cells isolated from type 1 diabetes patients and healthy donors.
Project description:Background: Mesenchymal stem cells (MSCs) have been widely used in the treatment of various inflammatory diseases. The inadequate understanding of MSCs and its heterogeneity can impact the immune environment maybe the cause of the good outcomes of MSCs-based therapy cannot be always achieved. Recently, stem cells from human exfoliated deciduous teeth (SHED) showed a great potential in inflammatory and autoimmune diseases due to its unique immunomodulation properties. However, the cellular heterogeneity and the corresponding immunomodulation functions of SHED remains unclear. Methods: In this study, we applied single-cell RNA sequencing (scRNA-seq) to analyze and performed bioinformatic analysis to clarify the variations immunomodulation functions of SHED subpopulations in different differentiation state. After the integration of public available databases, we analyzed the transcriptome and compared the difference of immunomodulation functions of MSCs from different tissues. Results: SHED in low differentiation state (S7) exhibited the powerful ability to recruit multiple types of immune cells, whereas SHED in relatively high differentiation state (S1) may hold strong ability to secret many factors with paracrine signaling capacity. Compared with human bone marrow derived mesenchymal stem cells (hBMSCs) or human umbilical cord-derived mesenchymal stem cells (hUCMSCs), SHED is stronger in immunomodulatory property, especially in recruitment of Th17, Th22 and Treg cells. Conclusion: SHED was a heterogeneous MSCs population with different differentiation states and immunomodulatory functions. SHED may have some advantages in treatment of inflammatory and autoimmune diseases. Our works provides some theoretical foundation for the SHED-based therapy in clinical applications.
Project description:We found that mesenchymal stem cells isolated from colonic tissue express significantly increased expression of Ptgs2 or cox-2 compared to that of mesenchymal stem cells isolated from the bone marrow, one of the most common tissues from which this cell type is derived. We hypothesized that the localization of these cells in the colon exposes them to specific environmental factors that induce and/or maintain increased constitutive levels of cox-2 uniquely in this cell type. In order to identify possible candidate molecules regulating cox-2 in these cells, we decided to compare the transcriptomes of colonic mesenchymal stem cells and bone marrow-derived mesenchymal stem cells.
Project description:Primary mouse bone marrow mesenchymal stromal cells (BM-MSCs) cultured for bone differentiation were exposed to vehicle (DMSO), synthetic RXR ligand (LG100268), type 2 diabetes therapeutic and PPARγ ligand (Rosiglitazone), and environmental PPARγ ligands (Tributyltin, Triphenyl Phosphate, and MEHP) to evaluate differential gene expression as well as nuclear receptor expression and downstream PPARG target gene expression between all chemical exposures
Project description:RNA-seq profiles of Wild Type or Prkcb-/- mouse bone marrow derived mesenchymal stromal cells (BMSCs), either monocultured or co-cultured with primary CLL cells.
Project description:Autoimmunity is often regarded as pathogenic, but this view has gradually shifted over time. Based on insights from thymus selection, T cells are now known to be selected by self-antigens and positive selection in the thymus medulla leads to regulatory functions. B cells are selected in the bone marrow and the fundamental question is whether self-antigens in the bone marrow select antigen specific regulatory B cells. In this work, we show that B cells are indeed selected for proteins expressed in the bone marrow and develop into cells with regulatory function bearing distinct phenotypic fingerprint. Collagen type II specific regulatory B cells trigger the expansion of antigen specific regulatory T cells and protect against development of tissue specific autoimmune inflammation. These antigen specific regulatory B cells constitute a sizeable fraction of the normal B cell repertoire in both mice and humans.
Project description:Pathological processes like osteoporosis or steroid-induced osteonecrosis of the hip are accompanied by increased bone marrow adipogenesis. Such disorder of adipogenic/osteogenic differentiation, which affects also bone marrow derived mesenchymal stem cells (BMSCs) contributes to bone loss during aging. Therefore, we investigated the effects of extracellular vesicles (EVs) isolated from human (h)BMSCs during different stages of osteogenic differentiation on osteogenic and adipogenic differentiation capacity of naïve hBMSCs.
Project description:We found that mesenchymal stem cells isolated from colonic tissue express significantly increased expression of Ptgs2 or cox-2 compared to that of mesenchymal stem cells isolated from the bone marrow, one of the most common tissues from which this cell type is derived. We hypothesized that the localization of these cells in the colon exposes them to specific environmental factors that induce and/or maintain increased constitutive levels of cox-2 uniquely in this cell type. In order to identify possible candidate molecules regulating cox-2 in these cells, we decided to compare the transcriptomes of colonic mesenchymal stem cells and bone marrow-derived mesenchymal stem cells. Mesenchymal stem cells were isolated by fast plastic adherence after collagenase type I-mediated dissociation of the tissue of origin. Cells were maintained in culture in low glucose DMEM with 10mM HEPES and 10% FBS. Cells were passaged at 90-100% confluency. Approximately 4 million cells from four MSC lines, two from colon and two from bone marrow, were lysed between passages 5 and 10. Total RNA was isolated, amplified, and hybridized to Affymetrix MOE230.2 chips.