2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucoside–stimulated dental pulp stem cells-derived exosomes for wound healing and bone regeneration

Background/purpose: -2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucoside (THSG) is a bioactive component in the Chinese herb Polygonum multiflorum, recognized for its anti-inflammatory and lipid-lowering properties. Human dental pulp stem cells (hDPSCs) have excellent capabilities in tooth regeneration, wound healing, and neural repair. The exosomes (Exo) released by hDPSCs contain bioactive molecules that influence cell proliferation, differentiation, and immune responses. Therefore, we aimed to unveil the potential of THSG-Exo and evaluate its regenerative capabilities through the in vitro experiment and rat bone defect model. Materials and methods: The effects of hDPSC-derived exosomes, with or without THSG treatment, on repair and bone regeneration were evaluated through in vitro and in vivo studies. Finally, we conducted a proteomic analysis to meticulously compare the compositional contents of the two types of exosomes. Results: In vitro data showed that 10 and 100 μM THSG-Exo enhanced cell proliferation and osteogenic differentiation, reducing wound size to 40 % of its original size. In our maxillary bone defect rat model, THSG-Exo significantly increased bone volume, trabecular thickness, and bone density in the bone defect area. In addition, proteomic analysis of THSG-Exo revealed diverse proteins linked to bone differentiation and tissue repair, including bone morphogenetic protein-1 (BMP-1) and tumor necrosis factor (TNF)-α-stimulated gene 6 (TNFAIP6). Our searches in functional databases revealed that THSG-Exo is involved in numerous biological pathways. Conclusion: THSG-Exo enhanced cell proliferation, wound healing, and osteogenesis in vitro, while also expediting tissue repair and bone regeneration in vivo. The protein diversity of THSG-Exo contributes significant value in both basic and regenerative medicine.