Pulp-dentin Regeneration

Abstract

The goal of regenerative endodontics is to reinstate normal pulp function in necrotic and infected teeth that would result in reestablishment of protective functions, including innate pulp immunity, pulp repair through mineralization, and pulp sensibility. In the unique microenvironment of the dental pulp, the triad of tissue engineering would require infection control, biomaterials, and stem cells. Although revascularization is successful in resolving apical periodontitis, multiple studies suggest that it alone does not support pulp-dentin regeneration. More recently, cell-based approaches in endodontic regeneration based on pulpal mesenchymal stem cells (MSCs) have demonstrated promising results in terms of pulp-dentin regeneration in vivo through autologous transplantation. Although pulpal regeneration requires the cell-based approach, several challenges in clinical translation must be overcome-including aging-associated phenotypic changes in pulpal MSCs, availability of tissue sources, and safety and regulation involved with expansion of MSCs in laboratories. Allotransplantation of MSCs may alleviate some of these obstacles, although the long-term stability of MSCs and efficacy in pulp-dentin regeneration demand further investigation. For an alternative source of MSCs, our laboratory developed induced MSCs (iMSCs) from primary human keratinocytes through epithelial-mesenchymal transition by modulating the epithelial plasticity genes. Initially, we showed that overexpression of ΔNp63α, a major isoform of the p63 gene, led to epithelial-mesenchymal transition and acquisition of stem characteristics. More recently, iMSCs were generated by transient knockdown of all p63 isoforms through siRNA, further simplifying the protocol and resolving the potential safety issues of viral vectors. These cells may be useful for patients who lack tissue sources for endogenous MSCs. Further research will elucidate the level of potency of these iMSCs and assess their transdifferentiation capacities into functional odontoblasts when transplanted into the root canal microenvironment.

Angiogenic Capacity of Dental Pulp Stem Cell Regulated by SDF-1α-CXCR4 Axis

“…Moreover, the proliferation potential of DPSCs is comparable to other types of MSC-like cells [1]. Despite the availability and the stemness of DPSCs, the potential applications and preclinical efficacy of DPSCs have been limited to the regeneration of pulp and dentin [42]. In this study, we further investigated the applicability of DPSCs in in vivo angiogenesis, which is one of the main huddles to overcome for successful tissue-engineered constructs.…”

Wnt and BMP signaling crosstalk in regulating dental stem cells: Implications in dental tissue engineering

“…Nonetheless, several pre-clinical human models demonstrated the potential utility of tissue engineering-based strategies in regenerating pulp–dentin complex, particularly for necrotic or immature permanent teeth 144 . A recent study using pulpal MSCs showed promising results in pulp–dentin regeneration in vivo through autologous transplantation, 145 reinforcing the notion that DPSCs may be used for successful dental tissue engineering 146 …”

Comparative Secretome Analysis of Mesenchymal Stem Cells From Dental Apical Papilla and Bone Marrow During Early Odonto/Osteogenic Differentiation: Potential Role of Transforming Growth Factor-β2

“…A novel treatment of pulp revascularization/regeneration is an effective approach for inducing root maturation (Iwaya et al, 2001;Banchs and Trope, 2004). During revascularization/regeneration procedures, the evoked-bleeding step leads to a substantial influx of stem cells from dental apical papilla (SCAPs) into the root canal, which contributes to root development and apical closure (Cao et al, 2015). However, several histological findings reported that most tissues formed in the canal of the revitalized immature permanent tooth lack organized pulp-dentin complex and consist of ectopic bone, fibrous tissues, and cementum (Martin et al, 2012;Saoud et al, 2015;Peng et al, 2017).…”

“…In some cases, the root canal space became partly obliterated with ectopic bone (Martin et al, 2012;Saoud et al, 2015). It is presumed that stem cells from alveolar bone would migrate into the root canal and initiate ectopic calcification deposition (Cao et al, 2015;Saoud et al, 2015). Mesenchymal stem cells (MSCs) from different dentoalveolar tissues are unique and retain identities from their direct tissue sources.…”