Mechanisms of Therapeutic Effects of Conditioned Media from Cultured Dental Pulp Stem Cells on Diabetic Polyneuropathy

Stem cell transplantation is expected to become a novel therapy for diabetic polyneuropathy. Dental pulp stem cells (DPSC) are an attractive cell source because they can be easily isolated from teeth extracted for general orthodontic reasons. We reported earlier that DPSC transplantation was effective for diabetic polyneuropathy. However, most of the transplanted DPSCs from this study are gone from the transplanted site and the mechanism of cell transplantation may have been due to the abundant secreted factors from stem cells. We confirmed that conditioned media from DPSCs (DPSC-CM) ameliorated diabetic polyneuropathy. We, therefore, examined the mechanism of therapeutic effects of DPSC-CM on diabetic polyneuropathy.

DPSCs were isolated and cultured from the mandibular incisors of 6-week-old male Sprague-Dawly (SD) rats. Diabetes was induced at 6-weeks by administering STZ. DPSC-CM was administered to the unilateral hindlimb skeletal muscles of both the diabetic and normal rats 8 weeks after the administration of STZ, and the measurements were performed 4 weeks after DPSC-CM administration. Administration of DPSC-CM significantly improved the delay of the sciatic nerve motor/sensory conduction velocity and reduced sciatic nerve blood flow in diabetic rats. TNF-α and CD68 gene expression in the sciatic nerves tended to increase in the diabetic group, which showed a decreasing trend by administration of DPSC-CM. Capillary density in the hindlimb skeletal muscle was decreased in diabetic rats. DPSC-CM significantly increased capillary/muscle ratio in the hindlimb skeletal muscles in the diabetic rats. It was revealed that intramuscular administration of DPSC-CM was effective for diabetic polyneuropathy at least in part by improving nerve/muscle blood flow and suppressing inflammation. These results indicate that DPSC-CM could be a novel therapy for diabetic polyneuropathy.