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Resume Les proprietes immunomodulatrices et anti-inflammatoires des cellules stromales mesenchymateuses sont la base de nombreux essais cliniques dans le monde entier. Un probleme majeur au developpement de cette therapie cellulaire est l’incapacite de predire la reponse ou l’echappement a ce type de traitement couteux. Grâce a l’utilisation combinee de techniques d’analyses transcriptomiques, proteomiques ou fonctionnelles menees sur du sang voire des biopsies tissulaires, il est possible de monitorer aux differentes etapes du traitement les modifications induites par la therapie sur une grande palette de parametres immunologiques. Ce type d’immunomonitoring pousse et standardise permettra, en lien avec l’analyse de la reponse clinique, de degager des biomarqueurs d’efficacite pertinents.

Background aims. Mesenchymal stromal cells (MSC) are the focus of research in regenerative medicine aiming at the regulatory approval of these cells for specific indications. To cope with the regulatory requirements for somatic cell therapy, novel approaches that do not interfere with the natural behavior of the cells are necessary. In this context in vivo magnetic resonance imaging (MRI) of labeled MSC could be an appropriate tool. Cell labeling for MRI with a variety of different iron oxide preparations is frequently published. However, most publications lack a comprehensive assessment of the noninterference of the contrast agent with the functionality of the labeled MSC, which is a prerequisite for the validity of cell-tracking via MRI. Methods.We studied the effects of iron oxide-poly(L-lactide) nanoparticles in MSC with flow cytom-etry, transmission electron microscopy (TEM), confocal laser scanning microscopy (CLSM), Prussian blue staining, CyQuant® proliferation testing, colony-forming unit-fibroblast (CFU-F) assays, flow chamber adhesion testing, immuno-logic tests and differentiation tests. Furthermore iron-labeled MSC were studied by MRI in agarose phantoms and Wistar rats. Results. It could be demonstrated that MSC show rapid uptake of nanoparticles and long-lasting intracellular persistence in the endosomal compartment. Labeling of the MSC with these particles has no influence on viability, differentiation, clonogenicity, proliferation, adhesion, phenotype and immunosuppressive properties. They show excellent MRI properties in agarose phantoms and after subcutaneous implantation in rats over several weeks. Conclusions. These particles qualify for studying MSC homing and trafficking via MRI.

Natural killer (NK) cells play an important role in the early innate response against cancer and infections whereas dendritic cells (DC) are critical in the initiation of adaptive immune responses through their unique antigen presentation capacities. It was discovered in 1999 by Fernandez et al. that DC and NK cells make functional interactions. In vitro, IL-12/IL-18, IL-15 and IFN-α/β production by activated DC enhance NK cell IFN-γ production, proliferation and cytotoxic potential, respectively. Activated NK cells induce DC maturation either directly or in synergy with suboptimal levels of microbial signals. NK cell-induced DC activation is dependent on both TNF-α/IFN-γ secretion and a cell–cell contact. Finally, immature DC appear susceptible to autologous NK cell-mediated cytolysis while mature DC are protected. Thus, the outcome of NK/DC cross-talk is likely to influence both innate and adaptive immune responses. In vivo, NK/DC interactions occur at least in lymphoid organs and promote Th1 differentiation. Thus, DC and NK cells are equipped with complementary sets of receptors that allow the recognition of various pathogenic agents, rendering the cross-talk between the two partners mandatory.