Project description:Bone marrow mesenchymal stromal cells (MSCs) regulate homeostasis and trafficking of cells of the blood lineage. In response to traumatic injury or infection, MSCs are believed to mobilize from the bone marrow, but it is largely unknown how egress into circulation impacts MSC function. Here we show that biomechanical forces associated with trafficking of MSCs from the bone marrow into the vasculature contribute uniquely to genetic signaling that reinforces MSC repression of immune cell activation. Laminar wall shear stress (LSS) typical of fluid frictional forces present on the lumen of arterioles stimulates increases in antioxidant and anti-inflammatory mediators, as well as an array of chemokines capable of immune cell recruitment. Importantly, LSS promotes a signaling cascade through COX2 that elevates prostaglandin E2 (PGE2) biosynthesis, permitting MSCs to suppress immune cell activation in the presence of inflammatory cues. Pharmacological inhibition of COX2 depleted PGE2 and impaired the ability of MSCs to block tumor necrosis factor-α (TNF-α) production, supporting a key role for PGE2 in the MSC immunomodulatory response to LSS. Preconditioning of MSCs by LSS ex vivo was an effective means of enhancing therapeutic efficacy in a rat model of traumatic brain injury, as evidenced by decreased numbers of apoptotic and M1-type activated microglia in the hippocampus and by retention of endogenous MSCs in the bone marrow. We conclude that biomechanical forces provide critical cues to MSCs residing at the vascular interface which influence MSC immunomodulatory and paracrine functions, thus providing unique opportunities for functional enhancement of MSCs used in therapeutic applications.
Project description:Mesenchymal stromal cells (MSCs) have been introduced as promising cell source for regenerative medicine. Besides their multilineage differentiation capacity, MSCs release a wide spectrum of bioactive factors. This secretome holds immunomodulatory and regenerative capacities. In intervertebral disc (IVD) cells, application of MSC secretome has been shown to decrease the apoptosis rate, induce proliferation and promote production of extracellular matrix (ECM). For clinical translation of secretome-based treatment, characterization of the secretome composition is needed to better understand the induced biological processes and identify potentially effective secretomes. Methods: This study aimed to investigate the proteome released by bone marrow derived MSCs following exposure to a healthy, traumatic, or degenerative human IVD environment by mass spectroscopy and quantitative immunoassay analyses. Exposure of MSCs to the proinflammatory stimulus interleukin 1β (IL-1b) was used as control.
Project description:The aim of the experiment is to compare the transcriptional profile of MEi (mesenchymal-like mucoepidermoid tumor) cells with BM-MSCs (bone marrow mesenchymal stromal cells). The MEi cells were isolated from a mucoepidermoid tumor from the trachea. BM-MSCs were isolated from bone marrow of healthy donors. The MEi cells are a new cell line established by Dr Lim Mei Ling.
Project description:Mesenchymal stem/stromal cells (MSCs) are skeletal stem cells capable of regenerating bone, cartilage, and adipose tissues, while also serving as an essential immunosupportive cell for the hematopoietic stem cell pool. Therefore, the isolation and purification of murine MSCs is essential to understanding the differentiation capabilities necessary for skeletal regeneration, hematopoietic support, and immunomodulatory roles of MSCs within the bone marrow microenvironment (BMME). While many protocols on isolation from bone marrow (BM-MSCs) and bone associated cells (BAC-MSCs) have been published, none achive purity from macropahge contamination and many do not address heterogeneity of MSCs between these two compartments. To ensure a pure MSC isolation, we established a new strategy to exclude macrophages and their precursors by targeting F4/80/Ly6C/CD45. By analyzing MSC transcriptional profiles from both compartments with and without our purification strategy, we demonstrated distinct functional characteristics of MSCs by compartment, as well as functional impacts on the MSC transcriptional profile as a result of macrophage interaction.
Project description:Mesenchymal stromal cells (MSCs) derived from bone marrow (BM) have stronger potential for endochondral ossification compared to white adipose tissue (WAT)-MSCs, umbilical cord (UC)-MSCs, and skin fibroblasts (FB). We assessed uniquely accessible enhancers facilitating bone regeneration potential.
Project description:In this study, we assessed the effects of lysyl oxidase (LOX/LOXL) inhibition on the composition of extracellular matrix (ECM) produced by in vitro expanded bone marrow derived mesenchymal stromal cells (MSCs) of n=3 patients with myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN).
Project description:Mesenchymal stromal cells (MSCs) derived from bone marrow (BM) have stronger potential for endochondral ossification compared to white adipose tissue (WAT)-MSCs, umbilical cord (UC)-MSCs, chondrocytes (CH) and skin fibroblasts (FB). We assessed active regulatory regions facilitating bone-regeneration potential.
Project description:Mesenchymal stromal cells (MSCs) are multipotent progenitors that can be isolated from different sources, such as the bone marrow, adipose tissue and umbilical cord. The therapeutic potential of MSCs is related to a plethora of immunomodulatory, anti-inflammatory and pro-repair actions, which are at least partially dependent on their secretome. Among the components of MSCs' secretome, EVs have received considerable attention because MSC-EVs exert similar therapeutic properties as their parent cells. Among the different MSC sources for EV production, human umbilical cord MSCs (hUCMSCs) show advantages such as tissue availability, high proliferative profile of the cells and potential beneficial therapeutic effects in a variety of different diseases, such as stroke This study aimed to provide novel insights for future hUCMSC-EVs research and treatment selection. We investigated the influence of the culture and harvesting conditions on the EV proteomic profile, productivity, surface markers expression and evaluated their in vivo biodistribution and toxicity.
Project description:Cell culture confluency affects gene expression profiles of human bone marrow-derived mesenchymal stromal cells (MSCs). High-confluency MSCs are enriched in pathways that confer them a more immunosuppressive phenotype as compared to low-confluency MSCs.
Project description:To characterize and compare XF-iMSC (XenoFree-induced Mesenchymal stem/stromal cells) and various types of MSCs (Adipose-, Bone marrow-, Unbilical cord-derived), we performed a transcriptome analysis of these MSCs
