Dental Pulp Stem Cell-Derived Intracellular Vesicles Inhibit OSCC by Delivering PTEN to Suppress PI3K/AKT/mTOR...

Area of Science:

• Oncology
• Regenerative Medicine
• Biotechnology

Background:

• Oral squamous cell carcinoma (OSCC) is a prevalent and aggressive malignancy with poor outcomes.
• Dental pulp stem cell-derived intracellular vesicles (DPSC-IVs) are emerging as potential therapeutic agents due to their low immunogenicity and ability to modify the tumor microenvironment.

Purpose of the Study:

• To investigate the therapeutic potential of DPSC-IVs in inhibiting OSCC progression.
• To explore the synergistic effects of DPSC-IVs combined with autophagy inhibition in OSCC treatment.

Main Methods:

• In vitro and in vivo experiments were conducted using OSCC models.
• DPSC-IVs were administered alone and in combination with 3-methyladenine (3-MA), an autophagy inhibitor.
• Mechanistic studies focused on the PI3K/AKT/mTOR pathway, mitochondrial stress, autophagy, and PTEN delivery.

Main Results:

• DPSC-IVs significantly inhibited OSCC progression, suppressing proliferation, invasion, and colony formation while promoting apoptosis.
• The combination of DPSC-IVs and 3-MA synergistically enhanced antitumor effects by suppressing the PI3K/AKT/mTOR pathway and inducing mitochondrial stress.
• DPSC-IVs were found to deliver PTEN into OSCC cells, inhibiting PI3K/AKT signaling and promoting mitophagy.

Conclusions:

• DPSC-IVs demonstrate significant potential as a therapeutic strategy for OSCC, acting through dual mechanisms.
• The combination therapy with autophagy inhibition offers enhanced efficacy and warrants further clinical investigation.
• DPSC-IVs represent a safe, scalable, and clinically translatable option for regenerative oncology in OSCC treatment.