Evaluating Clinical Applications of Dental Stem Cells for Regeneration of Periodontal, Pulpal, and Craniofacial Tissues in Patients – A Systematic Review

Abstract

Background: Stem cell–based regenerative dentistry has emerged as a promising frontier in oral health care, offering biological alternatives to conventional restorative and surgical interventions. Despite extensive preclinical research demonstrating the regenerative potential of dental stem cells, clinical translation remains limited due to variability in methodologies and inconsistent long-term outcomes. Therefore, a comprehensive evaluation of current evidence is required to assess the efficacy, safety, and translational readiness of dental stem cell therapies for periodontal, pulpal, and craniofacial tissue regeneration. Objective: This systematic review aimed to evaluate the clinical applications, therapeutic efficacy, and safety of dental stem cell–based regenerative therapies in the regeneration of periodontal, pulpal, and craniofacial tissues. Methods: Following PRISMA 2020 guidelines, a systematic search was conducted across PubMed, Scopus, Web of Science, and the Cochrane Library for studies published between 2015 and 2025. Eligible studies included randomized controlled trials, observational studies, and systematic reviews focusing on human or translational animal models. Data extraction included study design, population, stem cell source, interventions, outcomes, and follow-up duration. The Cochrane Risk of Bias Tool and Newcastle–Ottawa Scale were used for quality assessment. Qualitative synthesis was performed, and quantitative data were analyzed using random-effects meta-analysis where appropriate. Results: Eight studies met the inclusion criteria, comprising both preclinical and clinical investigations. Dental pulp stem cells (DPSCs) and periodontal ligament stem cells (PDLSCs) demonstrated significant improvements in bone regeneration, pulpal vitality, and periodontal attachment. Pooled data showed a mean clinical attachment gain of 1.05 mm (95% CI −0.88–2.97) and a bone volume increase of 69.3 ± 3.9 mm³, with no major adverse events reported. Although outcomes favored stem cell therapy, heterogeneity among studies limited the strength of conclusions. Conclusion: Dental stem cell–based regenerative therapies exhibit strong potential for functional regeneration of dental and craniofacial tissues, demonstrating both efficacy and safety. However, variations in study design and limited long-term data necessitate further large-scale, standardized clinical trials to confirm therapeutic reliability and optimize translational protocols