Advances in combined application of dental stem cells and small-molecule drugs in regenerative medicine

Teeth are a kind of masticatory organs of special histological origin, unique to vertebrates, playing an important role in chewing, esthetics, and auxiliary pronunciation. In the past decades, with the development of tissue engineering and regenerative medicine, the studies of mesenchymal stem cells (MSCs) gradually attracted the interest of researchers. Accordingly, several types of MSCs have been successively isolated in teeth or teeth-related tissues, including dental pulp stem cells, periodontal ligament stem cells, stem cells from human exfoliated deciduous teeth, dental follicle stem cells, stem cells from apical papilla and gingival mesenchymal stem cells. These dental stem cells (DSCs) are easily accessible, possess excellent stem cell characteristics, such as high proliferation rates and profound immunomodulatory properties. Small-molecule drugs are widely used and show great advantages in clinical practice. As research progressed, small-molecule drugs are found to have various complex effects on the characteristics of DSCs, especially the enhancement of biological characteristics of DSCs, which has gradually become a hot issue in the field of DSCs research. This review summarizes the background, current status, existing problems, future research directions, and prospects of the combination of DSCs with three common small-molecule drugs: aspirin, metformin, and berberine.