ESPEYB20 1. Thyroid Thyroid Development (1 abstracts)
1.4. Transplantable human thyroid organoids generated from embryonic stem cells to rescue hypothyroidism
Romitti M , Tourneur A , de Faria da Fonseca B , Doumont G , Gillotay P , Liao XH , Eski SE , Van Simaeys G , Chomette L , Lasolle H , Monestier O , Kasprzyk DF , Detours V , Singh SP , Goldman S , Refetoff S & Costagliola S
Nat Commun. 2022 Nov 17;13(1):7057. doi: 10.1038/s41467-022-34776-7. PMID: 36396935
Brief summary: In recent years, generation of human organoids of different tissues from human embryonic stem cells have been realized, e.g. intestine, liver, and lung among others. In contrast, so far all attempts to generate fully mature and functional human thyroid follicular cells from stem cells was not successful. Romitti et al. present for the first time successful generation of transplantable and functional human thyroid organoids derived from human embryonic stem cells.
The Costagliola team has published in 2012 the generation of functional thyroid tissue derived from murine embryonic stem cells (1). Based on their experience, it took them ten years to establish a robust model to generate fully mature and functional human thyroid organoids. They report in detail on the doxycycline inducible transient overexpression of NKX2-1 and PAX8 in their human embryonic stem cell NKX2-1WT/GFP line. Subsequent differentiation steps as proliferation and maturation were then induced by addition of cAMP, hrTSH, and dexamethasone in the culture until stem cells became mature thyroid follicular cells. These thyroid follicular cells were analyzed extensively by immunohistochemistry, single cell RNA sequencing, and biochemistry to prove structural and functional differentiation with full synthetic capacity. Sequential single cell analysis over the whole culture period of 45 days documented in detail the changing gene expression pattern until reaching fully mature thyroid follicular cell expression. Immunohistochemistry showed mature follicular structure with expression of thyroperoxidase and thyroglobulin. Finally, the authors provided evidence for stable thyroid hormone synthesis of these human thyroid organoids after transplantation into mice that underwent radioablation of their thyroids and were hypothyroid. T3 levels in transplanted mice were completely normalized.
In conclusion, this extensive and elegant work is an important step forward in thyroidology. It opens avenues first, for detailed studies of human thyroid development not accessible by other models, and second, options for possible regenerative medicine in patients with thyroid diseases in the future.
Reference: 1. Generation of functional thyroid from embryonic stem cells. Antonica F, Kasprzyk DF, Opitz R, Iacovino M, Liao XH, Dumitrescu AM, Refetoff S, Peremans K, Manto M, Kyba M, Costagliola S. Generation of functional thyroid from embryonic stem cells. Nature. 2012 Nov 1;491(7422):66–71. doi: 10.1038/nature11525. Epub 2012 Oct 10. PMID: 23051751.
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ESPE Yearbook of Paediatric Endocrinology
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