Mesenchymal Stromal Cells Engage Complement and Complement Receptor Bearing Innate Effector Cells to Modulate Immune Responses

Infusion of human third-party mesenchymal stromal cells (MSCs) appears to be a promising therapy for acute graft-versus-host disease (aGvHD). To date, little is known about how MSCs interact with the body's innate immune system after clinical infusion. This study shows, that exposure of MSCs to blood type ABO-matched human blood activates the complement system, which triggers complement-mediated lymphoid and myeloid effector cell activation in blood. We found deposition of complement component C3-derived fragments iC3b and C3dg on MSCs and fluid-phase generation of the chemotactic anaphylatoxins C3a and C5a. MSCs bound low amounts of immunoglobulins and lacked expression of complement regulatory proteins MCP (CD46) and DAF (CD55), but were protected from complement lysis via expression of protectin (CD59). Cell-surface-opsonization and anaphylatoxin-formation triggered complement receptor 3 (CD11b/CD18)-mediated effector cell activation in blood. The complement-activating properties of individual MSCs were furthermore correlated with their potency to inhibit PBMC-proliferation in vitro, and both effector cell activation and the immunosuppressive effect could be blocked either by using complement inhibitor Compstatin or by depletion of CD14/CD11b-high myeloid effector cells from mixed lymphocyte reactions. Our study demonstrates for the first time a major role of the complement system in governing the immunomodulatory activity of MSCs and elucidates how complement activation mediates the interaction with other immune cells

Development of a sustainable catalytic ester amidation process

We describe the development of a sustainable ester amidation process. Base and solvent screening, combined with the application of Design of Experiments methodology was employed to identify an optimized set of reaction conditions using a sustainable protocol. Utilizing these optimized conditions, treatment of a range of ester derivatives with amino alcohols in the presence of a catalytic quantity of potassium phosphate deploying iso-propanol as solvent results in the highly efficient generation of a range of amido-alcohol derivatives in good to excellent yield, accompanied with excellent reaction mass efficiency (RME)

A global approach for the optimisation of batch reaction-separation processes

International audienceOptimisation of fine chemistry syntheses is often restricted to a dissociated approach of the process, lying in the separated determination of optimal conditions of each operating step. In this paper, a global approach of syntheses optimisation is presented. Focusing on the propylene glycol synthesis, this study highlights the benefits and the limits of the proposed methodology compared with a classical one

Optimisation of a Methyl Acetate Production Process by Reactive Batch Distillation

International audienceA general framework for the dynamic simulation and optimisation of global batch synthesis has been developed. In this paper, its application to the optimisation of a methyl acetate production process by reactive batch distillation is presented. Experiments performed on a batch pilot plant allow validating the dynamic model. Hence, optimal tuning of the operating parameters of the reactive batch distillation has been investigated by means of the dynamic optimisation procedure

Optimisation of global pharmaceutical syntheses integrating environmental aspects

International audiencePharmaceutical synthesis optimization, because of its complexity, is often reduced to the optimization of the reaction step. This chapter discusses the dynamic model, allowing simulating the different synthesis steps and, particularly start-up and shut-down phases involved. This model connected to an optimization method is able to provide the optimal operating conditions satisfying a global objective. The application to an industrial process highlights the benefits of the proposed methodology. The chapter describes the operating conditions involving the optimization of the global synthesis, satisfying economical and environmental criteria, to develop sustainable methodologies. For this purpose, a framework based on a simulation program, modeling a global synthesis (reaction and separation steps), has been developed. Besides global synthesis treatment, the main features of this work lie in the modeling of batch units and of dynamics, particularly during the start-up and the shut-down involved in the different step