Stem Cell Secretome Reverse Areca Nut Extract Induced Fibrosis in Human Fibroblast and Patient-Derived Biopsies.

Area of Science:

• Biomedical Science
• Regenerative Medicine
• Oral Pathology

Background:

• Oral submucous fibrosis is a progressive, potentially malignant oral condition linked to areca nut consumption.
• It significantly impacts oral cavity health and function.
• Current treatments are limited, necessitating novel therapeutic strategies.

Purpose of the Study:

• To investigate the potential of dental pulp mesenchymal stem cells secretome (DPMSCs-S) in reversing areca nut-induced oral fibrosis.
• To evaluate the effects of DPMSCs-S on human fibroblast cells and patient-derived buccal mucosa tissues.
• To identify the mechanisms underlying the secretome's therapeutic effects.

Main Methods:

• DPMSCs-S cytokine and growth factor levels were analyzed via flow cytometry.
• Cell viability, apoptosis, senescence, and reactive oxygen species (ROS) were assessed in human fibroblast cells.
• Fibrosis-related gene and protein expression (COL15A1, COL1, COL3, α-SMA, TGFβ1, TGFβ2) were evaluated using RT-PCR and fluorescence microscopy.

Main Results:

• Areca nut extract and arecoline reduced cell viability and induced apoptosis and senescence.
• DPMSCs-S treatment counteracted these effects, decreasing cell death, senescence, and ROS levels.
• Significant downregulation of fibrosis-related genes (COL15A1, COL3, α-SMA, TGFβ2) and COL1 protein expression was observed.
• Ex vivo studies confirmed reduced fibrosis markers in patient tissues treated with DPMSCs-S.

Conclusions:

• DPMSCs-S demonstrated significant cytoprotective and anti-fibrotic properties.
• The secretome effectively reduced cell death, senescence, collagen expression, and oxidative stress.
• DPMSCs-S shows potential as a novel therapeutic agent for oral submucous fibrosis, warranting further clinical investigation.