Introduction

In regenerative medicine, mesenchymal stem cells (MSCs) have garnered extensive attention because of their self-renewal and multi-differentiation abilities. Dental pulp stem cells (DPSCs), a type of MSCs found in dental pulp tissue, possess unique advantages and characteristics. In recent years, many studies have centered on the functional research of DPSCs. Given that DPSCs are considered an ideal cell source for dental pulp regeneration and have broad application prospects, they are gradually emerging as a new hope for reshaping oral tissues.

Mechanisms of DPSCs

The regeneration mechanism of DPSCs is mainly associated with their stem cell characteristics and secreted bioactive factors. DPSCs promote the regeneration and repair of host cells via a series of cell signaling pathways, including the Wnt signaling pathway, BMP/TGF-β signaling pathway, and Notch signaling pathway. Simultaneously, DPSCs can be regulated and differentiated into various cell types such as odontoblasts, osteoblasts, and nerve cells. Additionally, biomarkers of DPSCs like CD29, CD44, CD146, and CD90 are often utilized to identify and isolate DPSCs. The expression of these biomarkers not only provides identification methods for research but also holds great significance for evaluating the function and activity of cells.

Fig.1 Characteristics of dental pulp stem cells (Kwack K.H., et al. 2022).

Benefits of DPSCs

DPSCs possess several unique advantages, making them ideal candidates for regenerative medicine. Firstly, they have abundant sources and are easy to collect. Generally, they can be extracted from wisdom teeth, deciduous teeth, or other extracted teeth and the acquisition process is relatively non-invasive. Secondly, DPSCs have strong self-renewal ability and multi-directional differentiation potential. They can proliferate for a long time in vitro and maintain stem cell characteristics. Finally, DPSCs show good immune tolerance and can reduce rejection reactions. They have effective immune regulatory functions and can inhibit immune rejection in various ways, such as regulating the proliferation of immune cells and the production of cytokines and participating in the regulation of inflammation, providing favorable conditions for stem cell therapy.

Application of DPSCs in Stomatology

DPSCs exhibit great application potential in the field of stomatology, including in teeth regeneration, periodontal tissue repair, and jaw and facial bone defect repair. 

Fig.1 Composition of the jaw bone and periodontal tissue (Zhao J., et al. 2023).

Teeth Regeneration

The dental pulp-dentin complex is a crucial structure for teeth as it maintains their strength and stability. DPSCs can differentiate into odontoblasts and subsequently form a new dental pulp-dentin complex, thereby strongly facilitating the repair and regeneration of damaged teeth. Research has demonstrated that after injecting the complex of poly L-lactic acid microsphere scaffold and DPSCs in a highly biomimetic in vivo model, type I collagen and dentin formation protein are abundantly expressed in the root canal, significantly promoting dentin regeneration. In clinical applications, DPSCs can be combined with biomaterials and implanted in the dentin defect area to achieve regenerative repair.

Periodontal Tissue Repair

DPSCs function in periodontal tissue restoration primarily through two pathways. Firstly, DPSCs can differentiate into periodontal tissue cells like cementoblasts and periodontal ligament cells, thus taking part in the repair and regeneration process of periodontal tissues. Secondly, DPSCs can secrete a variety of growth factors and cytokines, such as vascular endothelial growth factor and bone morphogenetic protein. These factors can stimulate surrounding cells to proliferate, differentiate, and migrate, thereby promoting the repair of periodontal tissues. A study has accomplished in vivo regeneration of periodontal tissues through the successful transplantation of stem cells from human exfoliated deciduous teeth (SHED) combined with dentin matrix. DPSCs can become an effective treatment approach to improve the periodontal health status of patients faced with periodontal diseases.

Jaw and Facial Bone Defect Repair

DPSCs show great potential in jaw bone regeneration and repair by secreting active components like exosomes, growth factors, cytokines, and extracellular matrix. Compared with MSCs, DPSCs can generate newer osteoids and have more widely distributed collagen fibers in alveolar bone reconstruction, accelerating early osteoid formation and enhancing late bone mineralization. Additionally, DPSCs have immune regulatory functions, creating a favorable microenvironment for inflammation repair like jaw osteomyelitis, inhibiting local inflammatory reactions, and inducing M2 polarization of bone marrow cells. Notably, extracellular vesicles secreted by DPSCs play a crucial role in osteoblast differentiation and development during bone regeneration by carrying miRNAs and other signaling molecules. Therefore, non-cellular therapies for DPSCs, such as using their extracellular vesicles or combining their secretomes with biomaterials, may be an effective way to repair bone defects in the future.

Conclusion

As a kind of promising adult stem cell, DPSCs have many advantages in stomatology. They can differentiate into cementoblasts, periodontal ligament cells, etc., and actively participate in the repair and regeneration of jawbone and periodontal tissues. DPSCs also secrete various active components and have immune regulatory functions, creating a favorable microenvironment for oral inflammation repair. Moreover, DPSCs show broad application potential in treating systemic diseases such as neurological, circulatory, internal medicine, orthopedic, and eye diseases. In conclusion, with their excellent regenerative ability, DPSCs bring new hope for oral tissue remodeling.