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Background  Adipose derived stem cells can be stimulated to produce a growth factor rich secretome which enhances axon regeneration. In this study we investigated the importance of exosomes, extracellular vesicles released by many different cell types, including stem cells and endogenous nervous system Schwann cells (SCs), on neurite outgrowth.    Methods  Adipose derived stem cells were differentiated towards a Schwann cell-like phenotype (dADSCs) by  in vitro  stimulation with a mix of factors (basic fibroblast growth factor, platelet derived growth factor-AA, neuregulin-1 and forskolin). Using a precipitation and low-speed centrifugation protocol the extracellular vesicles were isolated from the medium of the stem cells cultures and also from primary SCs. The conditioned media or concentrated vesicles were applied to neurons  in vitro  and computerised image analysis was used to assess neurite outgrowth. Total RNA was purified from the extracellular vesicles and investigated using qRT-PCR.    Results  Application of exosomes derived from SCs significantly enhanced  in vitro  neurite outgrowth and this was replicated by the exosomes from dADSCs. qRT-PCR demonstrated that the exosomes contained mRNAs and miRNAs known to play a role in nerve regeneration and these molecules were up-regulated by the Schwann cell differentiation protocol. Transfer of fluorescently tagged exosomal RNA to neurons was detected and destruction of the RNA by UV-irradiation significantly reduced the dADSCs exosome effects on neurite outgrowth. In contrast, this process had no significant effect on the SCs-derived exosomes.    Conclusions  In summary, this work suggests that stem cell-derived exosomes might be a useful adjunct to other novel therapeutic interventions in nerve repair.

Schwann cell-like differentiated adipose stem cells promote neurite outgrowth via secreted exosomes and RNA transfer