Dental Pulp Mesenchymal Stem Cell‐Secretome Gel Reverse Areca Nut Induced Oral Submucous Fibrosis in Mice: A Pilot Study

Objectives Oral submucous fibrosis is a pre‐malignant disorder caused by habitual areca nut consumption. This pilot study investigated the therapeutic potential of dental pulp mesenchymal stem cell‐secretome chitosan gel in a mice model of areca nut extract‐induced oral submucous fibrosis. Materials and Methods Angiogenic potential of dental pulp mesenchymal stem cell‐secretome was validated using a chick yolk sac membrane assay. Oral submucous fibrosis was induced in male Swiss albino mice ( n = 40) via intraoral areca nut extract administration for 3 months. Post‐induction, animals were divided into disease control, DPMSCs‐S, and DPMSCs‐S gel groups. Treatments were administered intraorally twice weekly for 1 month. Therapeutic efficacy was assessed through measurements of mouth opening, histopathology, oxidative stress markers (LDH, MDA, SOD), and fibrotic gene expression (COL1, COL3, α‐SMA). Results Dental pulp mesenchymal stem cells’ secretome contains pro‐angiogenic growth factors. Dental pulp mesenchymal stem cells’ secretome gel significantly improved mouth opening, restored epithelial architecture, and reduced collagen deposition. Histological staining and gene expression analyses confirmed the reversal of fibrosis and downregulation of COL1, COL3, and α‐SMA. Additionally, the gel reduced LDH and MDA levels and enhanced SOD activity, indicating antioxidant effects. The gel showed superior efficacy over the secretome alone. Conclusion DPMSCs‐S gel demonstrates significant anti‐fibrotic, antioxidant, and regenerative potential in reversing ANE‐induced OSMF in mice. These findings warrant further investigation into larger, long‐term preclinical studies.