Development and primary characterization of a human thyroid organoid in vitro model for thyroid metabolism investigation
A 3D thyroid model was developed to address the limitations of 2D cultures and study the effects of compounds like 3-MNT on dehalogenase 1 (IYD) and metabolic activity. Morphology was assessed by TEM, and the expression of tissue-specific genes (TPO, TSHR, PAX8, TTF-1, NIS, IYD, TG) and metabolic features were analyzed using qRT-PCR, immunofluorescence, western blotting, ELISA, and LC-MS/MS, with and without TSH stimulus and 3-MNT treatment. Confocal and TEM analyses confirmed a follicle-like 3D structure. Expression of TPO, NIS, TG, TSH, and PAX markers was significantly higher (p < 0.05) in 3D versus 2D cultures, and ELISA showed increased TG protein production. 3-MNT treatment inhibited IYD activity, indicated by increased MIT and DIT in the media, and significantly altered (p < 0.05) NIS, TG, IYD, TSHR, and TPO expression. These findings suggest 3D thyroid cultures closely replicate tissue traits and functionality, providing a valuable tool for thyroid research.
Authors
- Federica Saponaro (ORCID: https://orcid.org/0000-0002-0277-1648)
- A Bertolini (ORCID: https://orcid.org/0000-0003-4810-7061)
- Vittoria Carnicelli
- Sandra Ghelardoni (ORCID: https://orcid.org/0000-0003-4378-5621)
- Maria Anita Giambelluca
- A. Sabbatini (ORCID: https://orcid.org/0000-0002-6375-7778)
- Sofia Cristiani
- Riccardo Zucchi (ORCID: https://orcid.org/0000-0002-6450-3788)
- Paola Lenzi (ORCID: https://orcid.org/0000-0002-4734-8798)
- Carlo Enrico Ambrosini (ORCID: https://orcid.org/0009-0005-9109-371X)
- Grazia Chiellini (ORCID: https://orcid.org/0000-0001-6703-5820)
- Ranieri Bizzarri (ORCID: https://orcid.org/0000-0002-8222-2672)
- Grazia Rutigliano (ORCID: https://orcid.org/0000-0001-6014-5357)
- Leonardo Rossi (ORCID: https://orcid.org/0000-0003-4974-3860)
- Gabriele Materazzi (ORCID: https://orcid.org/0000-0002-3040-516X)
- Francesco Fornai (ORCID: https://orcid.org/0000-0002-3883-5084)
- Alessandro Saba (ORCID: https://orcid.org/0000-0003-0611-5549)
- Valentina Vitelli (ORCID: https://orcid.org/0009-0009-2024-230X)
- L. Contu
Institutions
- University of Pisa (IT)
- Istituti di Ricovero e Cura a Carattere Scientifico (IT)
- Azienda Ospedaliera Universitaria Pisana (IT)
Publication Details
- Journal
- Molecular and Cellular Endocrinology
- Published
- 2024-09-27
- DOI
- https://doi.org/10.1016/j.mce.2024.112377
- Citations
- 4
- Primary Topic
- Thyroid Disorders and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 1.43
Funders
- Università di Pisa