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Bone marrow stromal cells (BMSCs) are capable of differentiating into various cell types including brain cells. Several groups have also demonstrated trophic effects of MSC grafts in experimental ischemia models. However, the underlying molecular mechanisms of these effects are not fully understood. We developed an ''in vitro graft model'' which consisted in a coculture of GFP-expressing BMSCs and hippocampal organotypic slice cultures. Total marrow cells (MCs) or BMSCs after one (BMSC 1P ) or five passages (BMSC 5P ) were transplanted on hippocampal slices. During the 10 days of our experiments, MCs and BMSC 1P migrated toward the tissue, but their total number remained constant. Conversely, the number of BMSC 5P decreased over the 10 days of the experiment, and no migration could be detected. Using immunohistochemistry, we observed that the hippocampal slices induced the expression of neural antigens in very few grafted cells, but MCs and BMSC 1P improved the conservation of the hippocampal slice culture. Similar experiments using BMSC 5P did not produce any significant change. We conclude that the number of passages greatly influence BMSCs survival rate, migration and neuroprotective capacities.

Neurodegenerative diseases represent a major public health issue and require better therapeutic management. The treatments developed mainly target neuronal activity. However, an inflammatory component must be considered, and microglia may constitute an important therapeutic target. Given the difficulty in developing molecules that can cross the blood–brain barrier, the use of food-derived molecules may be an interesting therapeutic avenue. Docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid (22:6 omega-3), has an inhibitory action on cell death and oxidative stress induced in the microglia. It also acts on the inflammatory activity of microglia. These data obtained in vitro or on animal models are corroborated by clinical trials showing a protective effect of DHA. Whereas DHA crosses the blood–brain barrier, nutritional intake lacks specificity at both the tissue and cellular level. Nanomedicine offers new tools which favor the delivery of DHA at the cerebral level, especially in microglial cells. Because of the biological activities of DHA and the associated nanotargeting techniques, DHA represents a therapeutic molecule of interest for the treatment of neurodegenerative diseases.

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