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Aims/Introduction  Dental pulp stem cells ( DPSC s) are thought to be an attractive candidate for cell therapy. We recently reported that the transplantation of  DPSC s increased nerve conduction velocity and nerve blood flow in diabetic rats. In the present study, we investigated the immunomodulatory effects of  DPSC  transplantation on diabetic peripheral nerves.    Materials and Methods   DPSC s were isolated from the dental pulp of Sprague–Dawley rats and expanded in culture. Eight weeks after the streptozotocin injection,  DPSC s were transplanted into the unilateral hindlimb skeletal muscles. Four weeks after  DPSC  transplantation, neurophysiological measurements, inflammatory gene expressions and the number of  CD 68‐positive cells in sciatic nerves were assessed. To confirm the immunomodulatory effects of  DPSC s, the effects of  DPSC ‐conditioned media on lipopolysaccharide‐stimulated murine macrophage  RAW 264.7 cells were investigated.    Results  Diabetic rats showed significant delays in sciatic nerve conduction velocities and decreased sciatic nerve blood flow, all of which were ameliorated by  DPSC  transplantation. The number of  CD 68‐positive monocytes/macrophages and the gene expressions of M1 macrophage‐expressed cytokines, tumor necrosis factor‐α and interleukin‐1β, were increased in the sciatic nerves of the diabetic rats.  DPSC  transplantation significantly decreased monocytes/macrophages and tumor necrosis factor‐α messenger ribonucleic acid expression, and increased the gene expression of the M2 macrophage marker,  CD 206, in the sciatic nerves of the diabetic rats. The  in vitro  study showed that  DPSC ‐conditioned media significantly increased the gene expressions of interleukin‐10 and  CD 206 in lipopolysaccharide‐stimulated  RAW 264.7 cells.    Conclusions  These results suggest that  DPSC  transplantation promoted macrophages polarization towards anti‐inflammatory M2 phenotypes, which might be one of the therapeutic mechanisms for diabetic polyneuropathy.

journal of diabetes investigation

Transplantation of dental pulp stem cells suppressed inflammation in sciatic nerves by promoting macrophage polarization towards anti‐inflammation phenotypes and ameliorated diabetic polyneuropathy