Potential application of dental stem cells in regenerative reconstruction of oral and maxillofacial tissues: a narrative review

Abstract

Background and objective: Oral and maxillofacial (OMF) defects caused by congenital conditions, injuries, ablative surgery for benign and malignant head & neck tumor, can often lead to OMF deformities and malfunctions in speech, mastication/chewing, and swallowing as well as have deleterious psychological effects and socioeconomic burdens to patients. Due to the unique complex 3D geometry of the head and neck region, reconstruction and rehabilitation of OMF defects remain a major challenge for OMF surgeons.The purpose of this narrative review is to update the information on the biological properties and functions of mesenchymal stem cells derived from various dental tissues (dental-MSCs) and their potential application in tissue engineering (TE) and regenerative reconstruction of OMF tissues.

Methods: A data-based search was performed by using PubMed database whereby articles published between 2000 and 2021 in English were included in the search with the following key words: dental stem cells, OMF reconstruction, OMF TE and regeneration.

Key content and findings: Currently, the advancement in stem cell biology, biomaterial science, and TE technology has demonstrated the significant potential application of stem cell-based therapy in regenerative reconstruction and rehabilitation of OMF defects. However, no stem cell-based product or device has been translated into clinical application to replace microsurgical free tissue transfer, the current mainstay of care in the reconstruction of OMF defects.

Conclusions: Currently, microsurgical free tissue transfer remains the gold standard mainstay of care for the reconstruction of OMF defects due to their abundant blood supply and flexibility for transplantation. However, several major challenges, such as the limited availability, the requirement of a second surgery, donor site morbidity, and the risk of free flap failure, have promoted the development of novel approaches. Due to the advancement in stem cell biology, biomaterial science, and TE technology, stem cell-based regenerative therapy is emerging as a promising therapeutic approach for a variety of diseases, including regenerative reconstruction and rehabilitation of OMF defects. In this narrative review, we update on the characteristics and biological functions of mesenchymal stem cells derived from various dental tissues (dental-MSCs) and their released cell-free products, extracellular vesicles (EVs). We also highlighted their potential application in TE and regenerative reconstruction of OMF defects in animal models and clinical studies and the potential challenges in this field.

Keywords: Dental stem cells; extracellular vesicles (EVs); oral and maxillofacial (OMF) defect; regenerative therapy; tissue engineering (TE).

Figure 1

Sources, properties, and biological functions of dental mesenchymal stem cells. Portions of this figure were made using templates from SMART SERVIER MEDICAL ART (https://smart.servier.com) and Biorender (https://biorender.com/). DPSC, dental pulp stem cells; SHED, stem cells from human exfoliated deciduous teeth; PDLSC, periodontal ligament stem cell; GMSC, gingiva-derived mesenchymal stem cell; SCAP, stem cells derived from apica papilla; DFSC, dental follicle stem cell; TGSC, tooth germ stem cell; OMF, oral and maxillofacial; CFU-f, colony forming unit-fibroblasts; CM, conditioned medium; EVs, extracellular vesicles; PBMC, peripheral blood mononuclear cell.

Figure 2

Potential application of dental MSCs and their cell-free products in tissue engineering and regenerative reconstruction of oral & maxillofacial tissue defects. Portions of this figure were made using templates from SMART SERVIER MEDICAL ART (https://smart.servier.com). MSC, mesenchymal stem cell; CM, conditioned medium; EVs, extracellular vesicles; TE/RM, tissue engineering/regenerative medicine.