Abstract

The recent advances in stem cell biology have raised great expectations that diseases and injuries of the central nervous system (CNS) may be ameliorated by the development of non-haematopoietic stem cell medicines. Yet, the application of stem cells as CNS therapeutics is very challenging and the interpretation of some of the outcomes is not completely unambiguous. In fact, the initial idea that stem cell transplants work only via structural cell replacement has been significantly challenged by the observation of consistent cellular signalling between the graft and the host. Cellular signalling is the foundation of coordinated actions and flexible responses and it is well established that this signalling takes place through different pathways involving networks of interacting molecules, which in turn transmit patterns of information between cells. 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 I will focus on the main cellular signalling pathways that grafted stem cells use to establish a therapeutically relevant cross talk with immune cells, examined the potential role of local inflammation in these communications, 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.