Dentin-Pulp Complex Regeneration

Advances in dental research

Dentistry is entering an exciting era in which many of the advances in biotechnology offer opportunities for exploitation in novel and more effective therapies. Pulp healing is complex and dependent on the extent of injury, among many other factors. Many of the molecular and cellular processes involved in these healing events recapitulate developmental processes. The regulation of odontoblast activity is clearly central to pulp healing, and an understanding of the mechanisms involved in these processes is necessary to enable laboratory studies to be translated to clinic application. Transcriptome analysis has identified changes in many odontoblast genes during the life-cycle of this cell and its responses to injurious challenge. The p38 MAPKinase pathway appears to be central to the transcriptional control of odontoblasts and may provide a key target for therapeutic intervention. The many recent advances in knowledge of pulpal stem cells and molecular signaling molecules within the ...

Archives of Oral Biology, 2005

Journal of Endodontics, 2017

Fibroblasts represent the most abundant population within the dental pulp. While other cell types such as odontoblasts and stem cells have been extensively investigated, very little attention was given to the fibroblasts which have major roles in regulating the pulp biology and function under normal and pathological conditions. Indeed, while pulp fibroblasts control the pulp vascularization and innervation under physiological conditions, these cells synthesize growth factors that enhance dentin-pulp regeneration, vascularization and innervation. Pulp fibroblasts also represent a unique cell population as it the only non-hepatic and non-immune cell type capable of synthesizing all complement proteins leading to production of biologically active fragments such as C3a, C5a and membrane attack complex (MAC) which play major roles in the pulp regeneration processes. C3a fragment is involved in inducing the proliferation of both stem cells and pulp fibroblasts. It is also involved in stem cell mobilization and pulp fibroblast recruitment. C5a, guides nerve sprouting and stem cell recruitment. The MAC complex fixes on cariogenic bacteria walls leading to their direct destruction. These data demonstrate the central role played by pulp fibroblasts in regulating the dentin-pulp tissue by directly destroying cariogenic bacteria and by releasing bioactive fragments involved in nerve sprouting and stem cell recruitment and pulp regeneration. Taken together, this shows that targeting pulp fibroblasts represents a realistic strategy to induce complete dentin-pulp regeneration.

Gene Therapy, 2006

Odontoblasts are postmitotic cells that differentiate from the dental papilla. These cells are responsible for producing the calcified dentin matrix. The pulp-odontoblast interphase contains undifferentiated mesenchymal stem cells, which have the ability to cytodifferentiate into odontoblast-like cells in response to specific signaling molecules. Dentin matrix protein 1 (DMP1) is one of the dentin noncollagenous extracellular matrix proteins that has been implicated in regulation of mineralization. In this study, we have examined the potential role of DMP1 in inducing cytodifferentiation of dental pulp stem cells into odontoblast-like cells and formation of reparative dentin in a rat model. Cavities were drilled and pulps exposed in maxillary first molars. Collagen matrix impregnated with recombinant DMP1 was implanted directly in Group 1, while calcium hydroxide, a commonly used pulp-capping agent was implanted in group 2, collagen matrix that was not impregnated with rDMP1 was implanted directly in group 3, which served as control. Each of these three groups was subdivided into two subgroups, A for 2 weeks time duration and B for 4 weeks duration. At the end of the time period the maxillae were excised, tissues were processed for histological and immunohistochemical evaluations. The results showed that DMP1 could act as a morphogen on undifferentiated mesenchymal cells present in the dentin-pulp complex. These differentiated cells had the potential to regenerate dentin-like tissue, which was confirmed by the presence of collagenous matrix, odontoblast specific markers and calcified deposits. Gene Therapy (2006) 13, 611-620.

Journal of Endodontics, 2014

The traditional concept of replacing diseased tooth/pulp tissues by inert materials (restoration) is being challenged by recent advances in pulp biology leading to regenerative strategies aiming at the generation of new vital tissue. New tissue formation in the pulp chamber can be observed after adequate infection control and the formation of a blood clot. However, differentiation of true odontoblasts is still more speculative, and the approach is largely limited to immature teeth with open apices. A more systematic approach may be provided by the adoption of the tissue engineering concepts of using matrices, suitable (stem) cells, and signaling molecules to direct tissue events. With these tools, pulplike constructs have already been generated in experimental animals. However, a number of challenges still remain for clinical translation of pulp regeneration (eg, the cell source [resident vs nonresident stem cells, the latter associated with cell-free approaches], mechanisms of odontoblast differentiation, the pulp environment, the role of infection and inflammation, dentin pretreatment to release fossilized signaling molecules from dentin, and the provision of suitable matrices). Transition as a process, defined by moving from one form of ''normal'' to another, is based not only on the progress of science but also on achieving change to established treatment concepts in daily practice. However, it is clear that the significant recent achievements in pulp biology are providing an exciting platform from which clinical translation of dental pulp regeneration can advance.

Journal of endodontics, 2008

Dental pulp cells (DPCs) are capable of differentiating into odontoblasts that secrete reparative dentin after pulp injury. The molecular mechanisms governing reparative dentinogenesis are yet to be fully understood. Here we investigated the differential protein profile of human DPCs undergoing odontogenic induction for 7 days. Using two-dimensional differential gel electrophoresis coupled with matrix-assisted laser adsorption ionization time of flight mass spectrometry, 23 protein spots related to the early odontogenic differentiation were identified. These proteins included cytoskeleton proteins, nuclear proteins, cell membrane-bound molecules, proteins involved in matrix synthesis, and metabolic enzymes. The expression of four identified proteins, which were heteronuclear ribonuclear proteins C, annexin VI, collagen type VI, and matrilin-2, was confirmed by Western blot and real-time real-time polymerase chain reaction analyses. This study generated a proteome reference map durin...

bioRxiv (Cold Spring Harbor Laboratory), 2024

Regeneration of dentin and odontoblasts from dental pulp stem cells (DPSCs) is essential for permanent tooth maintenance. However, the in vivo identity and role of endogenous DPSCs in reparative dentinogenesis are elusive. Here, using pulp single-cell analysis before and after molar eruption, we revealed that endogenous DPSCs are enriched in Cxcl12-GFP + coronal papilla-like cells with Mx1-Cre labeling. These Mx1 + Cxcl12-GFP + cells are long-term repopulating cells that contribute to the majority of pulp cells and new odontoblasts after eruption. Upon molar injury, Mx1 + DPSCs localize into the injury site and differentiate into new odontoblasts, forming scleraxis-GFP + and osteocalcin-GFP + dentinal tubules and reparative dentin. Single-cell and FACS analysis showed that Mx1 + Cxcl12-GFP + DPSCs are the most primitive cells with stem cell marker expression and odontoblast differentiation. Taken together, our findings demonstrate that Mx1 labels postnatal DSPCs, which are the main source of pulp cells and new odontoblasts with reparative dentinogenesis in vivo.

Advances in Dental Research, 2011

Mesenchymal stem cells are present in the dental pulp. They have been shown to contribute to dentin-like tissue formation in vitro and to participate in bone repair after a mandibular lesion. However, their capacity to contribute efficiently to reparative dentin formation after pulp lesion has never been explored. After pulp exposure, we have identified proliferative cells within 3 zones. In the crown, zone I is near the cavity, and zone II corresponds to the isthmus between the mesial and central pulp. In the root, zone III, near the apex, at a distance from the inflammatory site, contains mitotic stromal cells which may represent a source of progenitor cells. Stem-cell-based strategies are promising treatments for tissue injury in dentistry. Our experiments focused on (1) location of stem cells induced to leave their quiescent state early after pulp injury and (2) implantation of pulp progenitors, a substitute for classic endodontic treatments, paving the way for pulp stem-cell-ba...

Journal of Hard Tissue Biology, 2006

Dentin extracellular matrix proteins display multifunctional properties. Firstly, they participate to the mineralization processes either as promotors or as inhibitors of crystal nucleation or crystal growth. Secondly, they act as signaling molecules implicated in the differentiation of odontoblast progenitors. These molecules may be used to promote the recruitment of odontoblast progenitors, the proliferation and the final differentiation into functional odontoblast-like or osteoblast-like cells implicated in pulp repair. This has been evaluated through a series of experiments carried out in vivo on the rat first maxillary molar and in vitro on odonto/osteo progenitors. Along this line, BMP7 (OP1) induced in the crown a fibrous osteodentin-like structure where unmineralized pulp remnants were seen. In addition, the mesial root canal was totally filled with a homogeneous dentin-like structure. The bone sialoprotein (BSP) stimulated within one month the formation of a reparative dentinal bridge and the complete closure of the coronal pulp with an atubular homogeneous reparative dentin. Dentonin, a peptide from MEPE, implantated into the exposed pulp produced more rapidly than the two previous molecules reparative mineralization in the coronal pulp and also occlusion of the lumen of the root canal. Implanted in the exposed pulp, A+4 and A-4, two spliced amelogenin gene products, induce either the formation of a reparative dentinal bridge (A+4) or a more diffuse mineralization (A-4). The mechanisms of proliferation and differentiation were studied in parallel in an in vivo situation after implantation in the first maxillary molar of the rat, and in vitro on odontoblast progenitor cell lines. These molecules may contribute to pulp repair and promote new strategies in dental therapies.

Journal of Bone Metabolism

Dental pulp stem cells (DPSCs) have garnered significant interest in dental research for their unique characteristics and potential in tooth development and regeneration. While there were many studies to define their stem cell-like characteristics and osteogenic differentiation functions that are considered ideal candidates for regenerating damaged dental pulp tissue, how endogenous DPSCs respond to dental pulp injury and supply new dentin-forming cells has not been extensively investigated in vivo. Here, we review the recent progress in identity, function, and regulation of endogenous DPSCs and their clinical potential for pulp injury and regeneration. In addition, we discuss current advances in new mouse models, imaging techniques, and its practical uses and limitations in the analysis of DPSCs in pulp injury and regeneration in vivo.