Clinical trials using dental stem cells: 2022 update

For nearly 20 years, dental stem cells (DSCs) have been successfully isolated from mature/immature teeth and surrounding tissue, including dental pulp of permanent teeth and exfoliated deciduous teeth, periodontal ligaments, dental follicles, and gingival and apical papilla. They have several properties (such as self-renewal, multidirectional differentiation, and immunomodulation) and exhibit enormous potential for clinical applications. To date, many clinical articles and clinical trials using DSCs have reported the treatment of pulpitis, periapical lesions, periodontitis, cleft lip and palate, acute ischemic stroke, and so on, and DSC-based therapies obtained satisfactory effects in most clinical trials. In these studies, no adverse events were reported, which suggested the safety of DSC-based therapy. In this review, we outline the characteristics of DSCs and summarize clinical trials and their safety as DSC-based therapies. Meanwhile, we also present the current limitations and perspectives of DSC-based therapy (such as harvesting DSCs from inflamed tissue, applying DSC-conditioned medium/DSC-derived extracellular vesicles, and expanding-free strategies) to provide a theoretical basis for their clinical applications.