Localization and chronological changes of the adult stem cells in the pulpal regeneration process after tooth replantation and transplantation

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Rodent incisors are known to be continuously growing teeth that are maintained by both the cell-proliferation at the apical end and the attrition of the incisal edge. We propose a new concept that the eternal tooth bud producing various dental progeny is formed at the apical end of continuously growing teeth, and a new term "apical bud" for indicating this specialized epithelial structure. Furthermore, BrdU labeling analysis suggested that the guinea-pig molars, which were continuously growing teeth, also possessed plural specific proliferative regions and "apical bud" at the apical end.The mechanism to determine the divergent pulpal healing process after tooth injury remains unclear. We investigated the healing process of dental pulp after tooth replantation by use of micro-computed tomography (μ-CT), immunocytochemistry for heat-shock protein (HSP)-25 and cathepsin K (CK), and histochemistry for both alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP), In control teeth at postnatal 4 weeks, the periphery of coronal dental pulp showed intense ALP-and HSP-25-positive reactions, whereas no TRAP-and CK-positive cells occurred there. Tooth replantation weakened or ceased ALP-and HSP-25-positive reactions in the pulp tissue at the initial stages. Three to seven days after operation, ALP-positive region recovered from the root apex to the coronal pulp followed by HSP-25-positive reactions in the successful case leading to tertiary dentin formation. In another case, TRAP-and CK-positive cells appeared in the pulp tissue of replanted tooth at postoperative days 5-10,and remained to be associated with the bone tissue after 12-60 days. These data suggest that the appearance of TRAP-and CK-positive cells may be a trigger to induce bone tissue formation in the dental pulp.