ABSTRACT Periodontitis, a prevalent inflammatory disease, leads to the destruction of periodontal tissues, and current treatments often fail to achieve complete regeneration. Stem cell‐derived exosomes, nanoscale vesicles mediating intercellular communication, have emerged as a promising cell‐free therapeutic approach. This study aimed to investigate the potential of exosomes derived from dental pulp mesenchymal stem cells (DP‐MSCs) and folic acid (FA), both individually and in combination, to improve periodontal injury in an in vitro model. DP‐MSCs were isolated from human deciduous teeth, cultured, and characterized by their differentiation potential into adipocytes and osteocytes, as well as flow cytometry analysis of mesenchymal stem cell markers. Exosomes were extracted from DP‐MSC conditioned media and characterized using scanning electron microscopy (SEM) and Bradford assay for protein quantification. Human gingival fibroblasts (hGFs) were cultured and subjected to an in vitro injury model by exposure to H 2 O 2 . The injured hGF cells were then treated with FA (50 µM) and/or DP‐MSC‐Exos (20 µg/mL). Expression of anti‐inflammatory, antioxidant, apoptotic, and osteogenic genes was measured using real‐time quantitative polymerase chain reaction (RT‐qPCR). DP‐MSCs exhibited fibroblastic morphology, differentiated into adipocytes and osteocytes, and expressed mesenchymal markers CD73 and CD90. SEM confirmed the spherical structure of the extracted exosomes, and the Bradford assay revealed a protein concentration of 850 µg/mL. In injured hGF cells, treatment with DP‐SC‐Exos significantly decreased the Bax/Bcl2 ratio ( p < 0.0001) and reduced the expression of antioxidant genes CATA, glutathione peroxidase (GPx), superoxide dismutase (SOD), and receptor‐interacting serine/threonine‐protein kinase 3 (RIPK3). FA treatment reduced IL‐6 and tumor necrosis factor‐alpha (TNF‐α) expression, whereas both FA and DP‐MSC‐Exos treatments resulted in diminished TGF‐β expression. DP‐MSC‐derived exosomes demonstrated a notable capacity to modulate gene expression in an in vitro periodontal injury model, particularly by reducing apoptotic and antioxidant gene expression. These findings suggest that exosomes hold promise as a potential therapeutic agent for periodontal regeneration, offering advantages over cell‐based therapies.
Zarei et al. (2026) studied this question.