Dental Pulp Regeneration in Dogs Using a Chemokine Receptor 3 Antagonist Without Transplantation of Dental Pulp Stem Cells

Abstract

Introduction: Our previous study showed that transplantation of dental pulp stem cells in combination with a chemokine receptor 3 (CCR3) antagonist into the root canals of aged dogs promoted dental pulp regeneration. In this study, we attempted to regenerate dental pulp in young dogs using a CCR3 antagonist without dental pulp stem cell transplantation.

Methods: The teeth of dogs were histologically evaluated 4 weeks after extraction of the pulp and administration of scaffold materials and CCR3 antagonist (KDH-136) into the root canal. The effects of KDH-136 on the inflammatory response of RAW264.7 cells were investigated in vitro. In addition, we also examined whether KDH-136 affected neurite outgrowth of PC12 cells.

Results: Application of KDH-136 resulted in the formation of dental pulp-like tissue. Furthermore, nerve and blood vessel regeneration were observed. KDH-136 suppressed chemokine production from RAW264.7 cells and promoted nerve growth factor-stimulated neurite outgrowth of PC12 cells.

Conclusions: CCR3 antagonists may be useful for developing novel methods of dental pulp regeneration that do not require transplantation of dental pulp stem cells.

Keywords: CCR3 antagonist; cell-free therapy; pulp regeneration.