Characterization of Monoamine Oxidases in Mesenchymal Stem Cells: Role in Hydrogen Peroxide Generation and Serotonin-Dependent Apoptosis

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Evaluation of alginate microspheres for mesenchymal stem cell engraftment on solid organ

Mesenchymal stem cells (MSCs) may be used as a cell source for cell therapy of solid organs due to their differentiation potential and paracrine effect. Nevertheless, optimization of MSC-based therapy needs to develop alternative strategies to improve cell administration and efficiency. One option is the use of alginate microencapsulation, which presents an excellent biocompatibility and an in vivo stability. As MSCs are hypoimmunogenic, it was conceivable to produce microparticles with [alginate-poly-L-lysine-alginate (APA) microcapsules] or without (alginate microspheres) a surrounding protective membrane. Therefore, the aim of this study was to determine the most suitable microparticles to encapsulate MSCs for engraftment on solid organ. First, we compared the two types of microparticles with 4 × 106 MSCs/ml of alginate. Results showed that each microparticle has distinct morphology and mechanical resistance but both remained stable over time. However, as MSCs exhibited a better viability in microspheres than in microcapsules, the study was pursued with microspheres. We demonstrated that viable MSCs were still able to produce the paracrine factor bFGF and did not present any chondrogenic or osteogenic differentiation, processes sometimes reported with the use of polymers. We then proved that microspheres could be implanted under the renal capsule without degradation with time or inducing impairment of renal function. In conclusion, these microspheres behave as an implantable scaffold whose biological and functional properties could be adapted to fit with clinical applications

Time-dependent release of growth factors from implant surfaces treated with plasma rich in growth factors

Abstract: Plasma rich in growth factors (PRGFs) technology is an autologous platelet-rich plasma approach that provides a pool of growth factors and cytokines that have been shown to increase tissue regeneration and accelerate dental implant osseointegration. In this framework, the spatiotemporal release of growth factors and the establishment of a provisional fibrin matrix are likely to be key aspects governing the stimulation of the early phases of tissue regeneration around implants. We investigated the kinetics of growth factor release at implant surfaces functionalized either with PRGFs or platelet-poor plasma and correlated the results obtained with the morphology of the resulting interfaces. Our main finding is that activation and clot formation favors longer residence times of the growth factors at the interfaces studied, probably due to their retention in the adsorbed fibrin matrix. The concentration of the platelet-derived growth factors above the interfaces becomes negligible after 2-4 days and is significantly higher in the case of activated interfaces than in the case of nonactivated ones, whereas that of the plasmatic hepatocyte growth factor is independent of platelet concentration and activation, and remains significant for up to 9 days. Platelet-rich plasma preparations should be activated to permit growth factor release and thereby facilitate implant surface osseointegration. V C 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 00A:000-000, 2012

Utilisation des cellules souches adultes dans le cadre de la thérapie cellulaire des organes solides (études des relations cellules greffées-environnement tissulaire)

TOULOUSE3-BU Sciences (315552104) / SudocSudocFranceF

Mesenchymal Stem Cells Promote Matrix Metalloproteinase Secretion By Cardiac Fibroblasts And Reduce Cardiac Ventricular Fibrosis After Myocardial Infarction.

International audienceRecent studies showed that mesenchymal stem cells (MSCs) transplantation significantly decreased cardiac fibrosis. However, the mechanisms involved in these effects are still poorly understood. In this work, we investigated whether the antifibrotic properties of MSCs involve the regulation of matrix metalloproteinases (MMPs) and matrix metalloproteinase endogenous inhibitor (TIMPs) production by cardiac fibroblasts.In vitro experiments showed that conditioned medium from MSCs decreased viability, alpha-SMA expression and collagen secretion of cardiac fibroblasts. These effects were concomitant to the stimulation of MMP-2/MMP-9 activities and MT1-MMP expression. Experiments performed with fibroblasts from MMP2-/- mice demonstrated that MMP2 plays a preponderant role in preventing collagen accumulation upon incubation with conditioned-medium from MSCs. Interestingly, we found that MSC-conditioned medium also decreased the expression of TIMP2 in cardiac fibroblasts. In vivo studies showed that intracardiac injection of MSCs in a rat model of post-ischemic heart failure induced a significant decrease in ventricular fibrosis. This effect was associated with the improvement of morphological and functional cardiac parameters.In conclusion, we showed that MSCs modulate the phenotype of cardiac fibroblasts and their ability to degrade extracellular matrix. These properties of MSCs open new perspective for understanding of the mechanisms of action of MSCs and anticipate their potential therapeutic or side effects

Epistémologies, théories et pratiques professionnelles en communication des organisations

Quels rapports les pratiques professionnelles entretiennent-elles avec les théories dans le domaine de la communication des organisations ? C’est cette question, ancienne et récurrente, dont la pertinence ne s’épuise pas en raison des évolutions qui touchent l’un et l’autre domaine, que le dossier du n° 40 d’Études de Communication aborde, et plus particulièrement à partir de deux entrées : d’une part les fertilisations croisées entre sciences et pratiques professionnelles et d’autre part, la place du paradigme constructiviste, prédominant aujourd’hui dans la recherche en communication des organisations, dans ce rapport des théories aux pratiques. En filigrane, c’est aussi ce que la pratique fait de la recherche qui est interrogé et particulièrement les implications fonctionnalistes des approches constructivistes. Increasing opportunities for meetings, exchanges, and occasional confrontations between practitioners and researchers in the field of organizational communication invite us to take stock of the reasons that encourage the various actors to collaborate. It also gives us the chance to address research issues of an epistemological, theoretical, and practical nature. This paper introduces the two parts in which the six contributions to this special issue are organized. While the first part explores cross-fertilization between theory and practice, the second questions the input provided by the adoption of constructivist epistemologies

Ex vivo pretreatment with melatonin improves survival, proangiogenic/mitogenic activity, and efficiency of mesenchymal stem cells injected into ischemic kidney.

International audienceBone marrow mesenchymal stem cells (MSCs) have shown great potential in cell therapy of solid organs. Approaches to improving the ability of grafted MSCs to survive and secrete paracrine factors represent one of the challenges for the further development of this novel therapy. In the present study, we designed a strategy of ex vivo pretreatment with the pineal hormone melatonin to improve survival, paracrine activity, and efficiency of MSCs. Using a rat model of acute renal failure, we showed that melatonin pretreatment strongly increased survival of MSCs after intraparenchymal injection. This effect was concomitant with overstimulation of angiogenesis, proliferation of renal cells, and accelerated recovery of renal function. To gain insight into the mechanisms involved in the effects observed in vivo, melatonin was tested in vitro on cultured MSCs. Our results show that through stimulation of specific melatonin receptors, melatonin induced an overexpression of the antioxidant enzyme catalase and superoxide dismutase-1 and increased the resistance of MSCs to hydrogen peroxide-dependent apoptosis. Compared with untreated cells, MSCs incubated with melatonin displayed a higher expression of basic fibroblast growth factor and hepatocyte growth factor. In addition, conditioned culture media from melatonin-treated MSCs stimulated tube formation by endothelial progenitor cells and proliferation of proximal tubule cells in culture. In conclusion, our results show that melatonin behaves as a preconditioning agent increasing survival, paracrine activity, and efficiency of MSCs. The use of this molecule for pretreatment of stem cells may represent a novel and safe approach to improving the beneficial effects of cell therapy of solid organs