Generation and Differentiation of Adult Tissue-Derived Human Thyroid Organoids

• DOI: 10.1016/j.stemcr.2021.02.011
• Publication Date: 2021-03-12T11:20:04Z
• Authors: Vivian M.L. Ogundipe; Andries H. Groen; Nynke Hosper; Peter W.K. Nagle; Julia Hess; Hette Faber; Anne L. Jellema; Mirjam Baanstra; Thera P. Links; Kristian Unger; John T.M. Plukker; Rob P. Coppes
• Keywords: EXPRESSION; STIMULATION; Adult; 0301 basic medicine; GENES; LONG-TERM; HORMONE REPLACEMENT; Thyroid Gland; MOUSE; Article; Tissue Culture Techniques; Mice; 03 medical and health sciences; Hypothyroidism; Biomarkers, Tumor; Animals; Humans; Cell Self Renewal; 0303 health sciences; Stem Cells; Hypothyroidism ; Regeneration ; Stem Cells ; Thyroglobulin ; Thyroid Cancer ; Thyroid-tissue-derived Organoids ; Xeno-transplanation; Cell Differentiation; IN-VITRO; EXPANSION; 3. Good health; Organoids; Disease Models, Animal; EMBRYONIC STEM-CELLS; SYSTEM

Total thyroidectomy as part of thyroid cancer treatment results in hypothyroidism requiring lifelong daily thyroid hormone replacement. Unbalanced hormone levels result in persistent complaints such as fatigue, constipation, and weight increase. Therefore, we aimed to investigate a patient-derived thyroid organoid model with the potential to regenerate the thyroid gland. Murine and human thyroid-derived cells were cultured as organoids capable of self-renewal and which expressed proliferation and putative stem cell and thyroid characteristics, without a change in the expression of thyroid tumor-related genes. These organoids formed thyroid-tissue-resembling structures in culture. (Xeno-)transplantation of 600,000 dispersed organoid cells underneath the kidney capsule of a hypothyroid mouse model resulted in the generation of hormone-producing thyroid-resembling follicles. This study provides evidence that thyroid-lineage-specific cells can form organoids that are able to self-renew and differentiate into functional thyroid tissue. Subsequent (xeno-)transplantation of these thyroid organoids demonstrates a proof of principle for functional miniature gland formation.