Oral mesenchymal stem cells: biological characteristics and emerging therapeutic applications

Mesenchymal stem cells (MSCs) originating from the oral cavity constitute an accessible and minimally invasive reservoir of multipotent progenitors with broad relevance in regenerative medicine. Within this heterogeneous family, dental pulp stem cells (DPSCs), stem cells from exfoliated deciduous teeth (SHEDs), dental follicle stem cells (DFSCs), periodontal ligament stem cells (PDLSCs), gingival MSCs (GMSCs), and stem cells from the apical papilla (SCAPs) have been extensively studied. These populations share key MSC characteristics: clonogenicity, self-renewal, multilineage differentiation, and a bioactive secretome, while displaying distinct biological signatures that influence their therapeutic applications. This review integrates findings from preclinical and early clinical studies focused on the molecular markers, functional attributes, and regenerative potential of oral MSCs. Attention was given to comparative analyses of their differentiation behaviors, immunomodulatory profiles, and interactions with biomaterials and molecular regulators. DPSCs and SHEDs demonstrate prominent neurogenic and osteogenic potential and release a secretome with neuroprotective and anti-apoptotic properties, supporting their use in disorders of the nervous system. DFSCs and PDLSCs possess strong osteogenic and cementogenic activity, combined with notable immunomodulation, making them suitable for periodontal and bone regeneration. GMSCs exhibit high proliferative efficiency, genomic stability, and robust anti-inflammatory actions, partly mediated by extracellular vesicles. SCAPs, residing in the apical papilla, maintain viability in inflamed environments and are pivotal in regenerative endodontics. Emerging evidence underscores the contribution of scaffolds and non-coding RNAs in enhancing the therapeutic performance of these cells across dento-alveolar, neuroregenerative, and immune-mediated conditions. A refined understanding of the distinctive properties and mechanisms of action of oral MSCs is essential for optimizing translational strategies and advancing toward standardized, predictable regenerative therapies in dentistry and related medical fields.