ESPE Yearbook of Paediatric Endocrinology

Stem Cell Reports. 2021;16:913–925. doi: 10.1016/j.stemcr.2021.02.011.

In analogy to historical data [1], the authors provide important proof of principle that adult thyroid tissues cultivated in vitro show self-renewal and differentiation capacities and might ultimately be of use for regenerative autologous transplantation back into the donor patient affected by hypothyroidism.

Over the last decade several pluripotent murine and human stem cell (SC) approaches have been established to produce differentiated thyroid follicular cells using thyroid transcription factor overexpression, directed differentiation, or combination of both (reviewed in detail by Posabella et al. [2]). However, the use of such pluripotent SC-derived thyroid follicular cells is limited by ethical and practical aspects.

Recently, the existence of adult thyroid SC in the murine and human thyroid gland have been shown opening potential avenues for autologous thyroid regeneration techniques [3,4]. Based on these results, and as proof of principle, Ogundipe et al. aimed at developing a patient derived thyroid organoid model with proliferative and differentiation capacity in vitro.

The authors established organoid protocols for murine and human adult thyroid tissue organoids, which showed proliferation, as well as structural and functional differentiation shown by follicle formation, expression of the key proteins of the thyroid hormone synthetic machinery, finally culminating in some thyroxin synthetic capacity after (xeno-) transplantation into mice. Even after one year, organoids did not dediffentiate or develop tumours.

Although representing an important step towards thyroid regeneration by overcoming biological and ethical hurdles of pluripotent SC approaches, the presented organoid model is so far limited in cell number. Further optimization of the model will be necessary.

Reference: 1. Martin A, Valentine M, Unger P, Lichtenstein C, Schwartz AE, Friedman EW, Shultz LD, Davies TF. Preservation of functioning human thyroid organoids in the scid mouse: 1. System characterization. J Clin Endocrinol Metab. 1993;77:305–10. doi: 10.1210/jcem.77.2.8345031.2. Posabella A, Alber AB, Undeutsch HJ, Droeser RA, Hollenberg AN, Ikonomou L, Kotton DN. Derivation of Thyroid Follicular Cells From Pluripotent Stem Cells: Insights From Development and Implications for Regenerative Medicine. Front Endocrinol (Lausanne). 2021;12:666565. doi: 10.3389/fendo.2021.666565.3. Thomas T, Nowka K, Lan L, Derwahl M. Expression of endoderm stem cell markers: evidence for the presence of adult stem cells in human thyroid glands. Thyroid. 2006;16:537–44. doi: 10.1089/thy.2006.16.537.4. Gianì F, Vella V, Nicolosi ML, Fierabracci A, Lotta S, Malaguarnera R, Belfiore A, Vigneri R, Frasca F. Thyrospheres From Normal or Malignant Thyroid Tissue Have Different Biological, Functional, and Genetic Features. J Clin Endocrinol Metab. 2015;100:E1168-78. doi: 10.1210/JC.2014-4163.