The Origin of Microglia Determines the Content of Exosomes and Biological Function

Background: It is interesting to know whether microglia cells migrating in different central brain system components, i.e. cortex or in the spinal cord, are subjected to the same maturation processes and share similar functional phenotypes which could account with peculiar pathologies. Methods: We used a combination of pan proteomic platform associated with systemic biology analyses, in order to investigate that microglial cells derived from cortex and spinal cord expressed different phenotypes upon the physiological or pathological conditions Findings: This difference was found in cells and in their secreted exosomes. Cortical microglia showed neurogenesis/tumorigenesis characteristics, the spinal cord microglia revealed mostly involvement in the modulation of the inflammatory response to injury. We confirmed these results by performing functional testing including neurite outgrowth assays, and 3D spheroid cultures, which was used for glioma proliferation analysis. Results indicated that microglia located at different CNS areas reveal not only diverse content but also differential biological functions. Thus, the origin of microglia affected the physio-pathological function. These results also indicate differences in which the glioma is more prevalent in the brain than in spinal cord. Conclusion: Taken together, we demonstrated that microglia cells produce exosomes which can be used as therapeutic nanoparticles in translational medicine either in cancer treatment or in regenerative medicine. In fact, exosomes issued from spinal cord microglia can be addressed for glioma treatment and the ones from cortex microglia for spinal cord or brain traumatic injuries. Microglia exosomes are clearly a new source of therapeutic agents. Funding Statement: This research was supported by a collaboration between the Fundamental and Applied Biology Mass Spectrometry Laboratory (MS) and grants from Ministere de L’Education Nationale, L’Enseignement Superieur et de la Recherche, INSERM, SIRIC ONCOLille Grant INCD) a-DGOS-Inserm 6041aa (IF) and Universite de Lille (AM), APVV 15-0613 (DC), Stefanik SK-FR-2015-0018 (DC, MS), ERANET Axon Repair (DC). Declaration of Interests: The authors declare no competing financial interests in this work. Ethics Approval Statement: The study was performed with the approval and according to the guidelines of the Institutional Animal Care and Use Committee of the Slovak Academy of Sciences and with the European Communities Council Directive (2010/63/EU) regarding the use of animals in Research, Slovak Law for Animal Protection No. 377/2012 and 436/2012.