Abstract
SummaryTotal 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.
Highlights
Hypothyroidism results from the lack of thyroid hormones due to thyroid surgery, external beam irradiation, agenesis, or thyroid autoimmunity
Hypothyroidism requires lifelong daily thyroid hormone replacement therapy consisting of levothyroxine (LT4)
Almost 10% of the adult patients suffer from persistent severe complaints, which are largely related to thyroid hormone replacement therapy and have a major impact on quality of life (Husson et al, 2013)
Summary
Hypothyroidism results from the lack of thyroid hormones due to thyroid surgery, external beam irradiation, agenesis, or thyroid autoimmunity. Thyroid hormones are essential for the development of several tissues such as the brain, skeletal muscles, and bones They are required for lipid metabolism, proper regulation of tissue maintenance, and thermogenesis (Visser, 2018). Insufficient levels of thyroid hormone lead to fatigue, feeling cold, constipation, and weight gain, whereas high levels could lead to cardiovascular diseases (Elnakish et al, 2015; Klein Hesselink et al, 2013) or increased osteoporosis (Gorka et al, 2013). This is even more critical in children, who need optimal thyroid hormone levels to support neurological development and growth. A form of regenerative medicine to restore normal thyroid function might be an attractive alternative to drug treatment
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