Advances in stem cell biology have raised great expectations that diseases of the central nervous system may be ameliorated by the development of non-haematopoietic stem cell medicines. Yet, the application of stem cells as therapeutics is challenging and the interpretation of some of the outcomes ambiguous. The initial idea that stem cell transplants work only via structural cell replacement has been challenged by the observation of consistent intercellular information exchange between the graft and the host. Sustained stem cell graft-to-host exchange of signals has led to remarkable trophic effects on endogenous brain cells and beneficial modulatory actions on innate and adaptive immune responses that ultimately promote the healing of the injured CNS. Among a number of promising candidate stem cell sources, mesenchymal/stromal stem cells (MSCs) and neural stem/precursor cells (NPCs) are being extensively investigated for their capacities to signal to the immune system upon transplantation in experimental CNS diseases.
Here, we focused on defining whether the form of cellular signalling mediated by extracellular membrane vesicles (EVs) exists for neural stem/precursor cells (NPCs), and on its molecular signature and functional relevance on target cells. We also investigated whether the EV cargo molecules are modulated by extracellular pro- or anti-inflammatory cytokines, determined the key elements responsible for this novel mechanism of EV-mediated intercellular communication, and finally reflected on the forthcoming challenges related to the translation of these exciting experimental proofs into ready-to-use clinical medicines for inflammatory CNS diseases.