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The aim of this review was to unveil the concept of the use of small-molecule compounds and growth factors modulating key signaling pathways to derive ECs from DSCs.

In addition, our preliminary study showed that stem cells from the apical papilla could be induced into EC-like cells using small-molecule compounds and growth factors. These EC-like cells expressed endothelial specific genes (CD31 and VEGFR2) and proteins (CD31, VEGF receptor 2, and vascular endothelial cadherin) as well as gave rise to vessel-like tubular structures invitro.

Our preliminary results suggest that chemical reprogramming might offer a novel way to generate EC-like cells from dental stem cells.

Our preliminary results suggest that chemical reprogramming might offer a novel way to generate EC-like cells from dental stem cells.

The maintenance of a stem cell pool is imperative to enable healing processes in the dental pulp tissue throughout life. As such, knowing mechanisms underlying stem cell self-renewal is critical to understand pulp pathophysiology and pulp regeneration. The purpose of this study was to evaluate the impact of stem cell factor (SCF) signaling through its receptor tyrosine kinase (c-Kit) on the self-renewal of human dental pulp stem cells (hDPSCs).

The hDPSCs were stably transduced with lentiviral vectors expressing shRNA-c-Kit or vector control. The impact of the SCF/c-Kit axis on hDPSC self-renewal was evaluated by using a pulpsphere assay in low attachment conditions and by evaluating the expression of polycomb complex protein Bmi-1 (master regulator of self-renewal) by Western blot and flow cytometry.

The c-Kit-silenced hDPSCs formed fewer pulpspheres when compared with hDPSCs transduced with control vector (P<.05). Evaluation of pulpsphere morphology revealed the presence of 3 distinct sphere types, ie, holospheres, merospheres, and paraspheres. Although c-Kit silencing decreased the number of holospheres compared with control cells (P<.05), it had no effect on the number of merospheres and paraspheres. Recombinant human stem cell factor (rhSCF) increased the number of holospheres (P<.05) and induced dose-dependent Bmi-1 expression in hDPSCs. As expected, the inductive capacity of rhSCF on Bmi-1 expression and fraction of Bmi-1-positive cells was inhibited when we silenced c-Kit in hDPSCs.

These results unveiled the role of SCF/c-Kit signaling on the self-renewal of hDPSCs and suggested that this pathway enables long-term maintenance of stem cell pools in human dental pulps.

These results unveiled the role of SCF/c-Kit signaling on the self-renewal of hDPSCs and suggested that this pathway enables long-term maintenance of stem cell pools in human dental pulps.Postnatal stem cells critically maintain tissue homeostasis and possess immense potential for tissue regeneration. These stem cells in the orofacial system were not identified until early 2000s when they were first found in the dental pulp and termed dental pulp stem cells (DPSCs). Isolated from either permanent or deciduous teeth, DPSCs were characterized to be highly clonogenic with multidifferentiation and neurovascular properties. Subsequent studies suggested that the origin of DPSCs may be associated with neural crest-derived cells and localized adjacent to neurovascular bundles as indicated by specific surface markers. DPSCs serve as key contributors to pulp homeostasis and injury repair. Mechanistic studies have revealed a fine-tuning regulatory network composed of both extrinsic and intrinsic factors that orchestrate fates of DPSCs. These findings have shaped our understanding of their biological nature as niche responsive progenitors. As we explore the potential of DPSCs in pulp regeneration, preclinical studies have developed diverse DPSC transplantation-based strategies, among which preconditioned DPSCs and DPSC aggregates have shown particular promise. Confirmed by recent clinical advances, DPSC transplantation after pulpectomy has successfully rebuilt the physiological pulp structure in situ functionalized with neurovascularization, indicating a novel regenerative approach for treating pulp diseases. Selleck Tofacitinib Here, we summarized the 20-year golden journey on DPSCs from the unprecedented discovery to current clinical breakthroughs, while also suggesting future directions and challenges regarding expansion of regenerative applications and evaluation of in vivo DPSCs in diseases and therapies. The historical perspective of this field will provide a blueprint for the stem cell research and enlighten principles for de novo organ regeneration.

This article seeks to provide a historical perspective on the development of the pulp biology and regeneration research field, especially through the activities of the International Association for Dental Research Pulp Biology and Regeneration research group, and to identify the importance of technological advances for both past and future directions of this research field.

Key questions needing to be addressed in this field (relating to stem cells, bacterial challenges, progression and control of inflammation, and the specificity of dentinogenic responses during regeneration) to facilitate significant progress are also considered.

Key questions needing to be addressed in this field (relating to stem cells, bacterial challenges, progression and control of inflammation, and the specificity of dentinogenic responses during regeneration) to facilitate significant progress are also considered.Vital pulp therapy (VPT) in mature permanent teeth with carious pulp exposure has been a matter of debate, with root canal therapy being the conventional standard of care. Previously reported negative outcomes for VPT in these teeth were based on data from studies that have used calcium hydroxide in direct pulp capping and partial and full pulpotomy. The introduction of hydraulic calcium silicate-based materials with sealing and bioactive potentials have opened a new era in VPT with more favorable results. Understanding the histopathology and histobacteriology of the cariously exposed pulp and the healing potential of the inflamed pulp could guide the decision-making process toward an ultraconservative management of these teeth. However, proper case selection, strict aseptic condition, capping material, and good coronal seal are crucial for long-term success.

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