Abstract

Since the first transplant of stem cells into the spinal cord of rodents in which an acute demyelinating lesion was induced, we have witnessed a spur of experimental cell-based transplantation approaches aimed at fostering biological and molecular mechanisms underlying CNS repair. New hopes have been recently raised by the encouraging preliminary results obtained by transplanting CNS -derived NPCs and bone marrow mesenchymal/stromal stem cells in rodents with experimental MS. However, most of the results with stem cells as therapeutic weapons for MS have consistently challenged the sole and limited view that stem cells therapeutically work exclusively throughout cell replacement. Indeed, the transplantation of somatic (non-hematopoietic) stem cells promotes substantial CNS repair via a number of bystander mechanisms, mainly exerted by undifferentiated stem cells releasing in vivo a milieu of tissue-trophic and immune modulatory molecules, whose release is likely to be temporally and spatially orchestrated by specific (micro)environmental cues. These molecules are indeed are pleiotropic and redundant in nature as well as ‘constitutively’ secreted by stem cells. In this view, the therapeutic plasticity of stem cell can be viewed as the capacity of stem cells to adapt their fate and function(s) to specific environmental needs occurring as a result of different pathological conditions. While further studies are certainly required to assess the overall safety, efficacy and in vivo therapeutic plasticity of NPCs, the great challenge for any future human application of NPC -based protocols in MS will be to develop more reliable and reproducible approaches optimizing both (tissue) trophic as well as immune regulatory capacities of stem cells for functional and anatomical rescuing of myelin architecture in MS patients. Detailed review of the most recent data on the highly peculiar immune regulatory stem cell signature will be here provided.