Dental pulp stem cells promote the recovery of spinal cord injury by regulating microglia polarization via JAK2/STAT3 signaling pathway.

The inflammatory response after spinal cord injury (SCI) is an important cause of the difficulty in neurological recovery, and the immune imbalance between M1/M2 microglia/macrophage is involved in the onset and progression of SCI. Dental pulp stem cells (DPSCs) was reported to possess anti-inflammatory and neurotrophin-releasing properties. We established rat SCI models and transplanted DPSCs into rats via microcarrier sheets. The hind limb motor function was detected, and the pathological changes of the injured spinal cord tissues were assessed. A series of experiments, including enzyme-linked immunosorbent assay, immunefluorescence staining, and quantitative real time polymerase chain reaction (qRT-PCR) were performed to observe the inflammatory changes and microglia/macrophage polarization between groups. Next, we co-cultured DPSCs with microglia BV2 using the lipopolysaccharide (LPS)-induced inflammation model in vitro. RNA sequencing, qRT-PCR, immunofluorescence staining and western blot were used to verify the effects of DPSCs on microglia polarization, and to further explore the underlying mechanisms. Our results showed that transplantation of DPSCs reduced the severity of SCI in rat models, promoted the polarization of microglia/macrophage from M1-type to M2-type. These effects were further validated in the LPS-induced inflammatory environment in vitro. In addition, JAK2/STAT3 signaling pathway may be involved in the regulation of microglia polarization by DPSCs. Collectively, these results indicate that promoting microglia M2 polarization mediated by DPSCs may be an effective way to treat SCI.