Therapeutic effects of conditioned medium of immortalized dental pulp stem cells from human exfoliated deciduous teeth against experimental autoimmune neuritis

Cell-free therapy using the conditioned medium (CM) of mesenchymal stem cells has attracted great interest in regenerative medicine due to its fewer ethical and safety concerns. Recently, we established an immortalized dental pulp stem cell line from human exfoliated deciduous teeth (SHED). Herein, we have investigated the therapeutic potentials of SHED-CM on the peripheral neuropathy of experimental autoimmune neuritis (EAN). This model was established by immunizing mice with the myelin protein zero peptide. Multiple administrations of SHED-CM from the day reaching around the peak of symptoms ameliorated significantly the clinical score with slightly recovered motor function. The administrations upregulated myelin basic protein (MBP) and a critical transcriptional factor for myelination EGR2 and phosphorylation of HGF receptor c-MET, but conversely downregulated the negative regulator c-JUN in the sciatic nerves, suggesting the augmentation of remyelination. Moreover, SHED-CM augmented the proliferation of mouse Schwann cell line IMS32 cells partly depending upon HGF, neuregulin 1, and bFGF. SHED-CM induced phosphorylation of c-MET and neuregulin 1 receptors ErbB2-4. In primary mouse Schwann cells, SHED-CM upregulated EGR2 and MBP and promoted the EGR2-mediated myelination. SHED-CM has potent therapeutic effects on the peripheral neuropathy of EAN by promoting the remyelination of Schwann cells possibly through EGR2 upregulation.