Mesenchymal stem cells (MSC) are of particular interest for their potential clinical use in tissue engineering as well capacity to reduce the incidence and severity graft-versus-host disease allogeneic transplantation. We have previously shown that MSC-mediated immune suppression acts via secretion soluble factor(s) induced upon stimulation. The aim this study was identify molecule(s) involved underlying mechanism(s). show murine MSC secrete high levels interleukin (IL)-6 vascular...

Background Based on their capacity to suppress immune responses, multipotent mesenchymal stromal cells (MSC) are intensively studied for various clinical applications. Although it has been shown in vitro that the immunomodulatory effect of MSCs mainly occurs through secretion soluble mediators, mechanism is still not completely understood. The aim present study was better understand mechanisms underlying suppressive vivo, using isolated from mice deficient production inducible nitric oxide...

Abstract Objective Adult mesenchymal stem cells (MSCs) represent promising tools for therapeutic applications such as tissue engineering and cellular therapy. Recent data suggest that, due to their immunosuppressive nature, MSCs may be of interest enhance allogeneic hematopoietic engraftment prevent graft‐versus‐host disease. Using a murine model rheumatoid arthritis (RA), this study investigated whether the properties could value inhibit reactive T in autoimmune diseases RA. Methods In mice...

Abstract The role of interleukin 1 receptor antagonist (IL1RA) in mediating the immunosuppressive effect mesenchymal stem/stromal cells (MSCs) has been reported several studies. However, how MSC-derived IL1RA influences host response not clearly investigated. We therefore derived MSCs from bone marrow knockout mice and evaluated their on different immune cell subsets. deficient (IL1RA−/−) or wild type (wt) inhibited to same extend proliferation T lymphocytes. On contrary, IL1RA−/− were less...

Currently available murine models to evaluate mesenchymal stem cell (MSC) differentiation are based on injection at ectopic sites such as muscle or skin. Due the importance of environmental factors capacities cells in vivo, we investigated whether peculiar synovial/cartilaginous environment may influence lineage specificity bone morphogenetic protein (BMP)‐2‐engineered MSCs. To this aim, used C3H10T1/2‐derived C9 MSCs that express BMP‐2 under control doxycycline (Dox)‐repressible promoter,...

Abstract Previous studies have reported that mesenchymal stem cells (MSC) may be isolated from the synovial membrane by same protocol as used for fibroblast cultivation, suggesting MSC correspond to a subset of adherent cell population, stromal compartment bone marrow (BM). The aims present study were, first, better characterize derived and, second, compare systematically, in parallel, MSC-containing populations BM and those synovium, using quantitative assays. Fluorescent-activated sorting...

Abstract Chondrogenesis is a process involving stem-cell differentiation through the coordinated effects of growth/differentiation factors and extracellular matrix (ECM) components. Recently, mesenchymal stem cells (MSCs) were found within cartilage, which constitutes specific niche composed ECM proteins with unique features. Therefore, we hypothesized that induction MSC towards chondrocytes might be induced and/or influenced by molecules from microenvironment. Using microarray analysis,...

Mesenchymal stem cells (MSC) are widely investigated for cell therapy purposes as support of hematopoietic transplantation, skeletal tissue regeneration, or a delivery system therapeutic agents in cancer. However, because their immunosuppressive capacities, we the effect MSC on development syngeneic tumors. The murine line C3H10T1/2 was coinjected with Renca adenocarcinoma B16 melanoma lines BALB/c mice. injection permitted growth allogeneic tumor and reduced delay appearance when were...

<h3>Background:</h3> Multipotent mesenchymal stromal cells (MSC) are of particular interest for their potential clinical use in cartilage engineering, but a consistent model is missing large animals. <h3>Objective:</h3> In the absence any detailed study reporting complete characterisation isolated from sheep bone marrow, we fully characterised adherent and developed pre-clinical engineering by implantation autologous MSC Merinos sheep. <h3>Methods:</h3> Ovine (oMSC) were expanded further...

Skeletal development and cartilage formation require stringent regulation of gene expression for mesenchymal stem cells (MSCs) to progress through stages differentiation. Since microRNAs (miRNAs) regulate biological processes, the objective present study was identify novel miRNAs involved in modulation chondrogenesis. We performed miRNA profiling miR-29a as being one most down-regulated during Using chromatin immunoprecipitation, we showed that SOX9 down-regulates its transcription....

Systemic sclerosis (SSc) is a rare intractable disease with unmet medical need and fibrosis-related mortality. Absence of efficient treatments has prompted the development novel therapeutic strategies, among which mesenchymal stem cells/stromal cells (MSCs) or progenitor stromal appear to be one most attractive options. The purpose this study was use murine model hypochlorite-induced SSc investigate systemic effects MSCs on main features diffuse form disease: skin lung fibrosis,...

Hypertrophic scars (HTS) are characterized by excessive amount of collagen deposition and principally occur following burn injuries or surgeries. In absence effective treatments, the use mesenchymal stem/stromal cells, which have been shown to attenuate fibrosis in various applications, seems interest. The objectives present study were therefore evaluate effect human adipose tissue-derived stem cells (hASC) on a pre-existing HTS humanized skin graft model Nude mice compare efficacy hASCs...

The signaling role of the Ca 2+ releaser inositol 1,4,5-trisphosphate (IP 3 ) has been associated with diverse cell functions. Yet, physiological significance IP in tissues that feature a ryanodine-sensitive sarcoplasmic reticulum remained elusive. generated by photolysis caged or purinergic activation phospholipase Cγ slowed down abolished autonomic spiking neonatal rat cardiomyocytes. Microinjection heparin, blocking dominant-negative fusion protein, anti-phospholipase antibody prevented...

Living cells exhibit multiple K+ channel proteins; among these is the recently reported atypical two-pore domain protein TREK-1. Most currents are modulated by neurohormones and under various pathological conditions. Here, in rat ventricular cardiomyocytes using whole-cell patch-clamp technique, we characterize for first time a native TREK-1-like current (ITREK) that activated ATP, purine agonist applied at micromolar range. This sensitive to arachidonic acid, intracellular acidosis,...

Multipotent mesenchymal stromal cells (MSC) display a high potential for the development of novel treatment strategies cartilage repair. However, pathways involved in their differentiation to functional non hypertrophic chondrocytes remain largely unknown, despite work on embryologic and identification key growth factors including TGFbeta, Hh, Wnt FGF. In this study, we asked if could identify specific biological networks common used (TGFbeta3 or BMP-2). To address question, DNA microarrays...

<h3>Objectives</h3> Mesenchymal stromal cells (MSC) are characterised by their capacity to suppress immune reactions. This function was reported be shared in vitro fibroblasts but role has been poorly investigated vivo. study explored whether isolated from skin may the host response a model of autoimmune disorder. <h3>Methods and Results</h3> It first confirmed that lack differentiate into osteoblasts or chondrocytes possess inhibit proliferation T lymphocytes. Fibroblasts also secrete...

Mesenchymal stem or stromal cells (MSC) are under investigation in many clinical trials for their therapeutic potential a variety of diseases, including autoimmune and inflammatory disorders. One the main sources MSCs is adipose tissue, which mainly obtained by manual liposuction using cannula linked to syringe. However, past years, number devices fat intended use have been commercialized but few papers compared these procedures terms vascular fraction (SVF) mesenchymal (ASC). The objective...

Purinergic stimulation of cardiomyocytes turns on a Src family tyrosine kinase–dependent pathway that stimulates PLCγ and generates IP3, breakdown product phosphatidylinositol 4,5–bisphosphate (PIP2). This signaling closely regulates cardiac cell autonomic activity (i.e., spontaneous Ca2+ spiking). PIP2 is phosphorylated 3′ by phosphoinositide 3–kinases (PI3Ks) belong to broad kinase isoforms. The PI3K, 3,4,5–trisphosphate, PLCγ. PI3Ks have emerged as crucial regulators many functions...

In the context of regenerative medicine, use RNA interference mechanisms has already proven its efficiency in targeting specific gene expression with aim enhancing, accelerating or, more generally, directing stem cell differentiation. However, achievement good transfection levels requires a vector. For vivo applications, synthetic vectors are an interesting option to avoid possible issues associated viral (safety, production costs, etc.). Herein, we report on design tripartite polyionic...

Human papilloma virus type 16 (HPV-16) is the HPV most frequently associated with cervical carcinoma in humans. For prevention or treatment of carcinoma, E6 and E7 oncoproteins appear to be good targets for vaccine-induced cytotoxic T lymphocytes (CTL). Lipopeptide vaccination an efficient way stimulating cellular responses. However, synthesize effective lipopeptides, it necessary define which epitopes are immunogenic. In this study we first determined that peptide 80 – 88 protein was...

Fibrous scaffolds prepared from original PLA multiblock copolymers designed to match ACL properties are associated with MSCs for ligament repair.