Schwann cell-derived exosomes communicate with dorsal root ganglia (DRG) neurons. The present study investigated the therapeutic effect of exosomes derived from healthy Schwann cells (SC-Exos) on diabetic peripheral neuropathy (DPN). We found that intravenous administration of SC-Exos to type II diabetic db/db mice with peripheral neuropathy remarkably ameliorated DPN by improving sciatic nerve conduction velocity and increasing thermal and mechanical sensitivity. These functional improvements were associated with the augmentation of epidermal nerve fibers, and remyelination of sciatic nerves. Quantitative RT-PCR and Western blot analysis of sciatic nerve tissues showed that the SC-Exo treatment reversed diabetes-reduced microRNA (miR)-21, -27a and -146a and diabetes-increased Semaphorin 6A (SEMA6A), Ras homolog gene family, member A (RhoA), phosphatase and tensin homolog (PTEN), and nuclear factor-κB (NF-κB). In vitro data showed that SC-Exos promoted neurite outgrowth of diabetic DRG neurons and migration of Schwann cells challenged by high glucose. Collectively, these novel data provide evidence that SC-Exos have a therapeutic effect on DPN in mice and suggest that SC-Exos modulation of miRs contribute to this therapy
