Exploring the Therapeutic Potential of Extracellular Vesicles Derived from hDPSCs in Thyroid Carcinoma

Introduction Thyroid carcinoma (TC) stands as the most rapidly proliferating form of endocrine-related cancer. Among its histological types, Papillary Thyroid Carcinoma (PTC) emerges as the most prevalent, while Anaplastic Thyroid Carcinoma (ATC) poses the most severe threat. Despite PTC generally boasting a favorable prognosis, 5-10% of cases may manifest metastases, detrimentally impacting patient outcomes. Conversely, the aggressive demeanor of ATC precipitates swift metastasis, significantly curtailing survival post-diagnosis. Despite strides in oncological research, effective treatments for aggressive TC remain elusive. Recent investigations into extracellular vesicles (EVs) sourced from human dental pulp stem cells (EV-hDPSCs) have unveiled promising therapeutic potential in reshaping tumor microenvironments and delivering therapeutic payloads. In this study, we scrutinized the molecular and functional repercussions of treating PTC cell lines BCPAP and TPC1, alongside ATC cell lines 8505c, HTH-83, and KTC-2, with EV-hDPSCs. Methods CTP and ATC cells underwent a 72-hour treatment with EV-hDPSCs obtained from conditioned medium. The transcriptional effects of EVs were assessed through RNA-seq and PCR array analysis. Functional assays encompassed various cellular processes, including cell viability (Live/Dead assay), proliferation (CellTrace Violet and CCK-8 assay), cell cycle (propidium iodide assay), migration (wound healing assay), invasion (Matrigel-coated transwell assay), and energy metabolism (DCFDAH and Mitotracker assay). Additionally, EV-hDPSCs were nano-carried with sorafenib (SFB), and cell viability following SFB-EV treatment was evaluated using the Annexin-7AAD assay. Results and Conclusions Despite observing transcriptional changes, particularly notable in ATC cell lines, functional assays revealed minimal differences between the treated and control groups. This suggests that the natural cargo of EVs does not substantially alter the behavior of PTC and ATC cells. Subsequent experimentation with sorafenib-loaded EVs (SFB) highlighted a specific decrease in viability observed in BCPAP cells, underscoring the potential of EVs as nanocarriers for drug delivery. These findings indicate that while hDPSC-derived EVs may not provoke significant alterations in the inherent behavior of PTC and ATC cells, they hold promise as vehicles for delivering therapeutic drugs, thereby warranting further investigation.