{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:07:42Z","timestamp":1787011662449,"version":"build-2736575974"},"reference-count":37,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,7,4]],"date-time":"2025-07-04T00:00:00Z","timestamp":1751587200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Butantan Foundation"},{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior\u2014Brasil (CAPES)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/ijms26136443","type":"journal-article","created":{"date-parts":[[2025,7,4]],"date-time":"2025-07-04T05:54:52Z","timestamp":1751608492000},"page":"6443","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Preclinical In Vitro Evaluation of Extracellular Vesicles from Human Dental Pulp Stem Cells for the Safe and Selective Modulation of Anaplastic Thyroid Carcinoma"],"prefix":"10.3390","volume":"26","author":[{"given":"Anderson Lucas","family":"Alievi","sequence":"first","affiliation":[{"name":"Postgraduate Program in Endocrinology and Metabology, Paulista School of Medicine of the Federal University of S\u00e3o Paulo (EPM\/UNIFESP), S\u00e3o Paulo 04023-062, SP, Brazil"},{"name":"Genetics Laboratory, Butantan Institute, S\u00e3o Paulo 05503-900, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelli Ramires","family":"Teixeira","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Endocrinology and Metabology, Paulista School of Medicine of the Federal University of S\u00e3o Paulo (EPM\/UNIFESP), S\u00e3o Paulo 04023-062, SP, Brazil"},{"name":"Genetics Laboratory, Butantan Institute, S\u00e3o Paulo 05503-900, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vitor Rodrigues","family":"da Costa","sequence":"additional","affiliation":[{"name":"Genetics Laboratory, Butantan Institute, S\u00e3o Paulo 05503-900, SP, Brazil"},{"name":"Department of Morphology and Genetics, Paulista School of Medicine of the Federal University of S\u00e3o Paulo (EPM\/UNIFESP), S\u00e3o Paulo 04023-062, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Kerkis","sequence":"additional","affiliation":[{"name":"Genetics Laboratory, Butantan Institute, S\u00e3o Paulo 05503-900, SP, Brazil"},{"name":"Department of Morphology and Genetics, Paulista School of Medicine of the Federal University of S\u00e3o Paulo (EPM\/UNIFESP), S\u00e3o Paulo 04023-062, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo Pinheiro","family":"Araldi","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Endocrinology and Metabology, Paulista School of Medicine of the Federal University of S\u00e3o Paulo (EPM\/UNIFESP), S\u00e3o Paulo 04023-062, SP, Brazil"},{"name":"Department of Morphology and Genetics, Paulista School of Medicine of the Federal University of S\u00e3o Paulo (EPM\/UNIFESP), S\u00e3o Paulo 04023-062, SP, Brazil"},{"name":"BioDecision Analytics Ltd., S\u00e3o Paulo 05713-510, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1038\/nrendo.2017.76","article-title":"Anaplastic Thyroid Carcinoma: From Clinicopathology to Genetics and Advanced Therapies","volume":"13","author":"Molinaro","year":"2017","journal-title":"Nat. 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