# Preclinical In Vitro Evaluation of Extracellular Vesicles from Human Dental Pulp Stem Cells for the Safe and Selective Modulation of Anaplastic Thyroid Carcinoma

## TL;DR

This study explores the use of extracellular vesicles from dental pulp stem cells to safely and selectively target anaplastic thyroid cancer cells in a lab setting.

## Contribution

The novel contribution is the preclinical evaluation of hDPSC-EVs as a non-cytotoxic, targeted therapy for anaplastic thyroid carcinoma.

## Key findings

- hDPSC-EVs were efficiently internalized by ATC cells and selectively inhibited migration and invasion without affecting cell proliferation or viability.
- qPCR analysis revealed cell line-specific gene expression changes, with FN1 showing context-dependent regulation across different ATC cell lines.
- hDPSC-EVs demonstrated consistent safety with no cytotoxic effects or tumorigenic behavior observed.

## Abstract

Anaplastic thyroid carcinoma (ATC) is a highly aggressive malignancy with poor prognosis and limited treatment options. Precision oncology seeks personalized therapies that selectively modulate tumor behavior, which is critical for improving patient outcomes. In this study, we evaluated the therapeutic potential of human dental pulp stem cell-derived extracellular vesicles (hDPSC-EVs) in three ATC cell lines (8505C, HTH83, KTC-2). Fluorescence and confocal microscopy confirmed the efficient, time-dependent internalization of hDPSC-EVs by ATC cells, with increased fluorescence intensity over 48 h. Functional assays revealed the selective inhibition of migration and invasion in a cell line-dependent manner, without affecting cell proliferation, viability, or tumorigenic traits, indicating a non-cytotoxic, context-specific modulation of tumor behavior. After 72 h of EV treatment, targeted qPCR of 92 cancer-related genes showed the strongest response in 8505C cells (24 genes; 16 up, 8 down), moderate changes in KTC-2 (16 genes; 14 up, 2 down), and few alterations in HTH83 (6 genes; 4 up, 2 down). Across all lines, FN1 emerged as a context-dependent target, downregulated in 8505C but upregulated in the other two. No broad pathway enrichment was observed, indicating the fine-tuning of key networks rather than wholesale reprogramming. Despite variations across cell lines, hDPSC-EVs consistently demonstrated no impact on cell proliferation and no evidence of cytotoxicity or tumorigenic behavior, with no adverse outcomes. These findings provide preclinical evidence for hDPSC-EVs as a promising, safe, and targeted therapeutic platform in precision oncology, particularly for aggressive cancers, like ATC, warranting further exploration in preclinical and clinical studies.