Stem Cells from Human Exfoliated Deciduous Teeth Improve Motor Function after Sciatic Nerve Injury Through Suppression of Inflammation

Abstract

Stem cell therapy employing stem cells from human exfoliated deciduous teeth (SHED) has demonstrated efficacy in treating peripheral nerve injury; however, the precise underlying mechanisms remain largely undefined. In this study, we investigated the effects of SHED on signal transducer and activator of transcription 3 (STAT3), a key mediator of inflammation following sciatic nerve injury (SNI). The left sciatic nerve was transected (cut group), sutured and wrapped with cellulose (suture group), or sutured and enveloped with SHED-soaked cellulose (SHED group). The L4–5 segments of the spinal cord were harvested up to 7 days post-SNI, and tissues were separated into ipsilateral and contralateral regions for molecular and immunohistochemical analyses. In the SHED group, the sciatic functional index showed significant improvement compared with the suture group beginning at 4 weeks postinjury, and tibialis anterior muscle mass was markedly restored at 12 weeks. STAT3 phosphorylation at Tyr⁷⁰⁵ (p-STAT3) was prominently elevated between 12 and 48 h post-SNI on the ipsilateral side, but not contralaterally. This phosphorylation was localized to motor neurons in the anterior horn and was substantially attenuated by SHED administration between 24 and 48 h postinjury. Moreover, interleukin (IL)-6 expression was significantly reduced at 12 h, while p-STAT3 and importin β1 levels were notably decreased between 12 and 24 h. Erk signaling was significantly activated in S100β-positive Schwann cells (SCs) on day 4 at the site of SNI in the SHED group. These results suggest that SHED mitigate neuroinflammation by suppressing IL-6 expression and modulating STAT3 activation, while concurrently enhancing remyelination through Erk signaling activation in SCs at the injury site. Collectively, these findings underscore the therapeutic promise of SHED as a potent and innovative intervention for peripheral nerve avulsion injuries.