Different effect of Mesenchymal Stem Cells on cultures of cortical and sensory neurons exposed to toxic stimuli

Mesenchymal Stem Cells (MSCs) are frequently proposed as potentially suitable for the regenerative therapeutic approach for several neurological diseases both of the central nervous system, such as Multiple Sclerosis, and at the same way also of the peripheral nervous system, thanks to their ability to increase neuronal survival and to release neurotrophic factors. Since there are great differences between neurons of the central and of the peripheral nervous system, in this study we have verified the existence of a different susceptibility of cortical and sensory neurons to the effect of MSCs after different toxic stimuli, in order to mimic the damages observed in some neurological diseases. For this aim we set up direct and indirect co-cultures of MSCs and cortical or sensory neurons previousl exposed to toxic doses of glutamate, as a paradigm of Multiple Sclerosis, or treated with two widely used chemotherapeutic drugs, cisplatin and paclitaxel, which induce peripheral neuropathies. On the same cells we evaluated also the effect of conditioned medium of MSCs, by using morphological and molecular analysis. Neuronal viability was assessed by MTT test and by count of viable cells. Our results demonstrated the protective action of MSC direct and indirect co-cultures only on sensory neurons previously exposed to the toxic agents, while conditioned medium was ineffective to rescue it. On the contrary MSCs failed at all to protect cortical neurons from the drugs used, and their conditioned medium further reduces neuronal viability. We are now investigating the putative interference of MSCs with apoptotic molecules in sensory neurons, while in cortical neurons we are evaluating the possible causes of MSC-medium toxicity by analyzing the factors released. The different effect of MSCs on cortical and sensory neurons protection observed in vitro may be not the same in vivo, where the environments differ, anyway, it suggests to address the use of MSCs against the diseases affecting the peripheral nervous system rather than the central one. This makes mandatory to further investigate the causes of the different response of neuronal populations to MSC treatment, in order to widen their potential use.