Immunosuppression by mesenchymal stem cells: mechanisms and clinical applications

Mesenchymal stem cells (MSCs) are multipotential nonhematopoietic progenitor cells that are isolated from many adult tissues, in particular from the bone marrow and adipose tissue. Along with their capacity for differentiating into cells of mesodermal lineage, such as adipocytes, osteoblasts and chondrocytes, these cells have also generated great interest for their ability to display immunomodulatory capacities. Indeed, a major breakthrough came with the finding that they are able to induce peripheral tolerance, suggesting they may be used as therapeutic tools in immune-mediated disorders. The present review aims at discussing the current knowledge on the targets and mechanisms of MSC-mediated immunosuppression as well as the potential use of MSCs as modulators of immune responses in a variety of diseases related to alloreactive immunity or autoimmunit

Innovation sociale, un fondement de l'entrepreneuriat : Cas de l'écosystème Marocain

At present, everyone agrees that in order to gain competitiveness, we must put the human being at the center of models of economic and social development since it constitutes the wealth of any country, and the key success factor on which all other competitive advantages are based. However, Morocco is one of the country’s suffering from the increase in social magnitudes, namely poverty, social injustice, vulnerability, fragility, underemployment, unemployment, social exclusion, etc. It should be noted that such social phenomena weigh heavily on its economy and their absorption remains difficult, hence the need to seek new alternatives to fill its needs. It is in this sense that social entrepreneurship and social innovation are seen as innovative solutions that generate a social, concrete and lasting impact for the benefit of people, especially those who are harmed and disadvantaged. They even allow the creation of wealth, professional integration and the response to social needs not or poorly fulfilled by the state. The purpose of this paper is, on the one hand, to conceptualize the key concepts that interest us in particular social entrepreneurship and social innovation while at the same time exposing the link between the two. On the other hand, explain the transition of innovation to its social form while detecting approaches to social innovation and, of course, some related schools, and finally, examples of Moroccan entities forming an ecosystem of this type of innovation and seeking to promote, disseminate and put it at the heart of all processes.     Classification JEL:  O35, L31 Type of article : Theoretical ResearchÀ l’heure actuelle, tous s’accordent à dire que pour gagner en compétitivité, il faut mettre l’être humain au centre des modèles de développement économique et social vu qu’il constitue la richesse de tout pays, ainsi que le facteur clé de succès sur lequel reposent tous les autres avantages compétitifs. Cependant, le Maroc fait partie des pays qui souffrent de l’accentuation des grandeurs sociales à savoir : la pauvreté, l’injustice sociale, la vulnérabilité, le sous-emploi, le chômage, l’exclusion sociale…etc. Il faut noter que de tels phénomènes sociaux pèsent lourd sur son économie et leur absorption demeure difficile, d’où la nécessité de rechercher de nouvelles alternatives permettant de combler ses besoins. C’est dans ce sens que l’entrepreneuriat social et l’innovation sociale sont considérés comme des solutions novatrices et génératrices d’un impact social, concret et durable au profit des populations, plus particulièrement celles lésées et défavorisées. Ils permettent même la création de la richesse, l’insertion professionnelle ainsi que la réponse à des besoins sociaux non ou mal satisfaits par l’état. L’objectif de ce papier est, d’une part, de conceptualiser les notions phares qui nous intéressent notamment l’entrepreneuriat social et l’innovation sociale tout en exposant le lien entre les deux. D’autre part, expliquer le passage de l’innovation vers sa forme sociale tout en décelant les approches de l’innovation sociale et bien évidemment certaines écoles y afférentes, et enfin exposer des exemples d’entités marocaines formant un écosystème de ce type d’innovation et cherchant à la promouvoir, à la diffuser et à la mettre au cœur de tous les processus.   Classification JEL:  O35, L31 Type de l’article : Article théoriqu

Polymer-based microparticles in tissue engineering and regenerative medicine

Different types of biomaterials, processed into different shapes, have been proposed as temporary support for cells in tissue engineering (TE) strategies. The manufacturing methods used in the production of particles in drug delivery strategies have been adapted for the development of microparticles in the fields of TE and regenerative medicine (RM). Microparticles have been applied as building blocks and matrices for the delivery of soluble factors, aiming for the construction of TE scaffolds, either by fusion giving rise to porous scaffolds or as injectable systems for in situ scaffold formation, avoiding complicated surgery procedures. More recently, organ printing strategies have been developed by the fusion of hydrogel particles with encapsulated cells, aiming the production of organs in in vitro conditions. Mesoscale self-assembly of hydrogel microblocks and the use of leachable particles in three-dimensional (3D) layer-by-layer (LbL) techniques have been suggested as well in recent works. Along with innovative applications, new perspectives are open for the use of these versatile structures, and different directions can still be followed to use all the potential that such systems can bring. This review focuses on polymeric microparticle processing techniques and overviews several examples and general concepts related to the use of these systems in TE and RE applications. The use of materials in the development of microparticles from research to clinical applications is also discussed

Toll-Like Receptor-3-Activated Human Mesenchymal Stromal Cells Significantly Prolong the Survival and Function of Neutrophils

n/

A Novel Compound C12 Inhibits Inflammatory Cytokine Production and Protects from Inflammatory Injury In Vivo

Inflammation is a hallmark of many diseases. Although steroids and cyclooxygenase inhibitors are main anti-inflammatory therapeutical agents, they may cause serious side effects. Therefore, developing non-steroid anti-inflammatory agents is urgently needed. A novel hydrosoluble compound, C12 (2,6-bis(4-(3-(dimethylamino)-propoxy)benzylidene)cyclohexanone), has been designed and synthesized as an anti-inflammatory agent in our previous study. In the present study, we investigated whether C12 can affect inflammatory processes in vitro and in vivo. In mouse primary peritoneal macrophages, C12 potently inhibited the production of the proinflammatory gene expression including TNF-α, IL-1β, IL-6, iNOS, COX-2 and PGE synthase. The activity of C12 was partly dependent on inhibition of ERK/JNK (but p38) phosphorylation and NF-κB activation. In vivo, C12 suppressed proinflammatory cytokine production in plasma and liver, attenuated lung histopathology, and significantly reduced mortality in endotoxemic mice. In addition, the pre-treatment with C12 reduced the inflammatory pain in the acetic acid and formalin models and reduced the carrageenan-induced paw oedema and acetic acid-increased vascular permeability. Taken together, C12 has multiple anti-inflammatory effects. These findings, coupled with the low toxicity and hydrosolubility of C12, suggests that this agent may be useful in the treatment of inflammatory diseases

IL-6-Dependent PGE2 Secretion by Mesenchymal Stem Cells Inhibits Local Inflammation in Experimental Arthritis

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 the secretion of soluble mediators, the mechanism is still not completely understood. The aim of the present study was to better understand the mechanisms underlying the suppressive effect of MSCs in vivo, using cells isolated from mice deficient in the production of inducible nitric oxide synthase (iNOS) or interleukin (IL)-6 in the murine model of collagen-induced arthritis. PRINCIPAL FINDINGS: In the present study, we show that primary murine MSCs from various strains of mice or isolated from mice deficient for iNOS or IL-6 exhibit different immunosuppressive potential. The immunomodulatory function of MSCs was mainly attributed to IL-6-dependent secretion of prostaglandin E2 (PGE2) with a minor role for NO. To address the role of these molecules in vivo, we used the collagen-induced arthritis as an experimental model of immune-mediated disorder. MSCs effectively inhibited collagen-induced inflammation during a narrow therapeutic window. In contrast to wild type MSCs, IL-6-deficient MSCs and to a lesser extent iNOS-deficient MSCs were not able to reduce the clinical signs of arthritis. Finally, we show that, independently of NO or IL-6 secretion or Treg cell induction, MSCs modulate the host response by inducing a switch to a Th2 immune response. SIGNIFICANCE: Our data indicate that mscs mediate their immunosuppressive effect via two modes of action: locally, they reduce inflammation through the secretion of anti-proliferative mediators, such as NO and mainly PGE2, and systemically they switch the host response from a Th1/Th17 towards a Th2 immune profile