Generation and differentiation of adult tissue-derived human thyroid organoids

Summary 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.
Graphical abstract
Highlights • Thyroid-organoid-derived cells can self-renew and form all tissue lineages • Thyroid organoids express putative stem cell markers and no tumor gene expression • Maturation of these organoids leads to formation of tissue-resembling mini-glands • (Xeno-)transplantation into hypothyroid mice regenerates thyroid-resembling tissue
In this article, Ogundipe and colleagues demonstrate that thyroid gland-derived cells can be cultured as organoids for a prolonged time and differentiate in vitro to form hormone-producing mini-glands. (Xeno-)transplantation of dissociated organoids into hypothyroid mice allows generation of hormone-producing tissue-resembling follicles. These findings indicate that thyroid-lineage-specific cells contain proliferative potential to form thyroid-derived organoids capable of generating functional tissue.