Current Perspectives on Mesenchymal Stem Cells as a Potential Treatment for Periodontal Diseases and Conditions

Periodontal diseases, including periodontitis and gingivitis, constitute a major global health burden, affecting over 1 billion people worldwide. These conditions typically initiate in adulthood and progress chronically, often exhibiting severe manifestations. The socioeconomic impact is particularly acute in low- and middle-income countries, where limited healthcare access exacerbates disease outcomes. Although conventional treatments provide symptomatic relief, they often fail to achieve complete tissue regeneration due to the complex pathophysiology of periodontal destruction. Mesenchymal stem cells (MSCs) have emerged as a transformative therapeutic strategy, demonstrating unique capabilities for immunomodulation, anti-inflammatory effects, and multipotent differentiation. Preclinical studies have documented MSC-mediated regeneration of periodontal ligaments, alveolar bone, and cementum through paracrine signaling and direct tissue integration. Clinical trials further substantiate their potential to improve key outcomes, including clinical attachment levels and probing depth reduction. However, five critical challenges require resolution for successful translation: (1) cellular source standardization, (2) mechanistic understanding of long-term efficacy, (3) safety and immunological profiling, (4) ethical and economic barriers, and (5) clinical translation barriers. This review systematically evaluates current evidence on MSC-based periodontal regeneration, analyzes these translational challenges, and provides strategic guidance for future research. By integrating fundamental science with clinical perspectives, this work advances the development of reliable MSC therapies for periodontal regeneration.