Mesenchymal stem cell-secreted superoxide dismutase promotes cerebellar neuronal survival.

It has been postulated that bone marrow-derived mesenchymal stem cells (MSCs) might be effective treatments for neurodegenerative disorders either by replacement of lost cells by differentiation into functional neural tissue; modulation of the immune system to prevent further neurodegeneration; and/or provision of trophic support for the diseased nervous system. Here we have performed a series of experiments showing that human bone marrow-derived MSCs are able to protect cultured rodent cerebellar neurons, and specifically cells expressing Purkinje cell markers, against either nitric oxide exposure or withdrawal of trophic support via cell-cell contact and/or secretion of soluble factors, or through secretion of soluble factors alone. We have demonstrated that MSCs protect cerebellar neurons against toxic insults via modulation of both the phosphatidylinositol 3-kinase/Akt and MAPK pathways and defined superoxide dismutase 3 as a secreted active antioxidant biomolecule by which MSCs modulate, at least in part, their neuroprotective effect on cerebellar cells in vitro. Together, the results demonstrate new and specific mechanisms by which MSCs promote cerebellar neuronal survival and add further evidence to the concept that MSCs may be potential therapeutic agents for neurological disorders involving the cerebellum.