Recently, various levels of success have been achieved in dental pulp and dentin regeneration using latest techniques such as pulp revascularization, stem cell transplantation and cell homing. These cutting-edge technologies utilize stem cell mobilization, homing and directional differentiation, stem cell sub-population isolation, expansion and transplantation, modification and optimization of biomaterials and/or synergetic effects of biological cues. The objective of this review is to identify approaches for clinical translation and improve the success rates of pulp regeneration. We will focus on either basic and clinical research progress of dental pulp revascularization, or translational challenges and strategies of stem cell transplantation and cell homing in dental pulp regeneration.

A tooth is a complex biological organ and consists of multiple tissues including the enamel, dentin, cementum and pulp. Tooth loss is the most common organ failure. Can a tooth be regenerated? Can adult stem cells be orchestrated to regenerate tooth structures such as the enamel, dentin, cementum and dental pulp, or even an entire tooth? If not, what are the therapeutically viable sources of stem cells for tooth regeneration? Do stem cells necessarily need to be taken out of the body, and manipulated ex vivo before they are transplanted for tooth regeneration? How can regenerated teeth be economically competitive with dental implants? Would it be possible to make regenerated teeth affordable by a large segment of the population worldwide? This review article explores existing and visionary approaches that address some of the above-mentioned questions. Tooth regeneration represents a revolution in stomatology as a shift in the paradigm from repair to regeneration: repair is by metal or artificial materials whereas regeneration is by biological restoration. Tooth regeneration is an extension of the concepts in the broad field of regenerative medicine to restore a tissue defect to its original form and function by biological substitutes.
Adult Stem Cells ; Animals ; Humans ; Regeneration ; Regenerative Medicine ; Signal Transduction ; Stem Cell Transplantation ; Tissue Engineering ; Tissue Scaffolds ; Tooth ; physiology

Both bone morphogenetic protein 2 (BMP2) and the wingless-type MMTV integration site (WNT)/β-catenin signalling pathway play important roles in odontoblast differentiation and dentinogenesis. Cross-talk between BMP2 and WNT/β-catenin in osteoblast differentiation and bone formation has been identified. However, the roles and mechanisms of the canonical WNT pathway in the regulation of BMP2 in dental pulp injury and repair remain largely unknown. Here, we demonstrate that BMP2 promotes the differentiation of human dental pulp cells (HDPCs) by activating WNT/β-catenin signalling, which is further mediated by p38 mitogen-activated protein kinase (MAPK) in vitro. BMP2 stimulation upregulated the expression of β-catenin in HDPCs, which was abolished by SB203580 but not by Noggin or LDN193189. Furthermore, BMP2 enhanced cell differentiation, which was not fully inhibited by Noggin or LDN193189. Instead, SB203580 partially blocked BMP2-induced β-catenin expression and cell differentiation. Taken together, these data suggest a possible mechanism by which the elevation of β-catenin resulting from BMP2 stimulation is mediated by the p38 MAPK pathway, which sheds light on the molecular mechanisms of BMP2-mediated pulp reparative dentin formation.
Bone Morphogenetic Protein 2 ; physiology ; Cell Differentiation ; physiology ; Dental Pulp ; cytology ; Humans ; MAP Kinase Signaling System ; Wnt Proteins ; metabolism ; beta Catenin ; metabolism