"Bone marrow stromal cells (BMSCs) have been shown to be neuroprotective after experimental ischemic stroke when given systemically. By this route of administration, however, over 99% of cells are trapped in lung, spleen and kidneys. This off-target distribution of BMSCs may result in serious ectopic side-effects thereby making their use in humans questionable.The applicant’s previous work has demonstrated that transplantation of BMSCs to the cerebrospinal fluid compartment (CSFC) reduces post-ischemic brain damage. The cells circulate in the CSFC, attach to ventricular walls and potentially undergo cell-host interactions. Nevertheless, their presence seems sufficient to provide suitable trophic support and promote tissue repair, suggesting a secretory mechanism of action (secretome). Whether the beneficial effect is solely due to the BMSCs secretome in the CSFC or to cross-talk mechanisms between BMSCs and the brain is not clarified. A better understanding of these potential modes of action offers a promising opportunity for future development of ""cell-free"" based therapy.In this project, we seek to go ahead by studying the CSFC secretome and the observed cell-host interactions of BMSCs after experimental stroke by using state-of-art techniques such as Laser Capture Microdissection and Mass Spectroscopy. The ultimate goal of the project is to determine whether a ""cell-free"" CSFC secretome, which is devoid of any cell-specific side-effects, recapitulates the effects of transplanted BMSCs.Taken together, this project will analyze the in vivo BMSCs-secretome after cerebral ischemia and will translationally demonstrate the pre-clinical proof-of-concept of a “cell-free” BMSCs therapy for stroke. Due to the high socioeconomic burden of stroke for Europe, novel and effective treatments are urgently needed."