GENERATION OF FUNCTIONAL NEURONS FROM ADULT HUMAN MUCOSAL OLFACTORY ENSHEATHING GLIA BY DIRECT LINEAGE CONVERSION

ABSTRACT A recent approach to promote central nervous system (CNS) regeneration after injury or disease is direct conversion of somatic cells to neurons. This is achieved by transduction of viral vectors that express neurogenic transcription factors. In this work we propose adult human mucosal olfactory ensheathing glia (hmOEG) as a candidate for direct reprogramming to neurons due to its accessibility and to its well-characterized neuro-regenerative capacity. After induction of hmOEG with the single neurogenic transcription factor NEUROD1, the cells under study exhibited morphological and immunolabeling neuronal features, fired action potentials and expressed glutamatergic and GABAergic markers. In addition, after engraftment of transduced hmOEG cells in mouse hippocampus, these cells showed specific neuronal labeling. Thereby, if we add to the neuro-regenerative capacity of hmOEG cultures the conversion to neurons of a fraction of their population through reprogramming techniques, the engraftment of hmOEG and hmOEG induced neurons could be a procedure to enhance neural repair after central nervous system injury.