From mitochondria to immune networks: new mesenchymal stem cell strategies to treat periodontitis

Periodontitis is a chronic inflammatory disease that damages periodontal tissues and is mainly caused by immune dysfunction. Current treatments, such as mechanical debridement and adjunctive antimicrobial, work poorly; periodontal surgery brings pain and complications.Mesenchymal stem cells (MSCs) have a powerful ability to regulate immune responses and great potential for tissue regeneration, thus attracting extensive attention in the field of periodontal treatment. However, in the microenvironment of chronic periodontal inflammation, the therapeutic effect of MSCs is severely inhibited. Recent studies show that MSCs can transfer mitochondria to change energy metabolism, thereby regulating immune cell differentiation and function, lowering local immune responses. Therefore, this review proposes an innovative strategy of treating periodontitis using mitochondrial transfer by MSCs. It explores how mitochondrial transfer helps restore energy metabolism, reduce oxidative stress, and regulate immune cell function. This approach may reshape the immune-metabolic network in the periodontal microenvironment, reduce local chronic inflammation, and promote periodontal tissue regeneration.With the development of new technologies, treatments based on mitochondrial transfer from MSCs are expected to become more accurate and efficient in future clinical applications. In addition, this review introduces the "organ-immune-metabolism" three-dimensional regeneration model, which integrates organ repair, immune regulation, and metabolic reprogramming. We hope this review may offer new therapeutic insights for researchers in oral biology and periodontists treating periodontitis and other immune-related diseases.