Search

Stem cell-based therapies to reconstitute in vivo organ function hold great promise for future clinical applications to a variety of diseases. Hypothyroidism resulting from congenital lack of functional thyrocytes, surgical tissue removal, or gland ablation, represents a particularly attractive endocrine disease target that may be conceivably cured by transplantation of long-lived functional thyroid progenitors or mature follicular epithelial cells, provided a source of autologous cells can be generated and a variety of technical and biological challenges can be surmounted. Here we review the emerging literature indicating that thyroid follicular epithelial cells can now be engineered in vitro from the pluripotent stem cells (PSCs) of mice, normal humans, or patients with congenital hypothyroidism. We review the in vivo embryonic development of the thyroid gland and explain how emerging discoveries in developmental biology have been utilized as a roadmap for driving PSCs, which resemble cells of the early embryo, into mature functional thyroid follicles in vitro. Finally, we discuss the bioengineering, biological, and clinical hurdles that now need to be addressed if the goals of life-long cure of hypothyroidism through cell- and/or gene-based therapies are to be attained.

Stem cell-based therapies to reconstitute in vivo organ function hold great promise for future clinical applications to a variety of diseases. Hypothyroidism resulting from congenital lack of functional thyrocytes, surgical tissue removal, or gland ablation, represents a particularly attractive endocrine disease target that may be conceivably cured by transplantation of long-lived functional thyroid progenitors or mature follicular epithelial cells, provided a source of autologous cells can be generated and a variety of technical and biological challenges can be surmounted. Here we review the emerging literature indicating that thyroid follicular epithelial cells can now be engineered in vitro from the pluripotent stem cells (PSCs) of mice, normal humans, or patients with congenital hypothyroidism. We review the in vivo embryonic development of the thyroid gland and explain how emerging discoveries in developmental biology have been utilized as a roadmap for driving PSCs, which resemble cells of the early embryo, into mature functional thyroid follicles in vitro. Finally, we discuss the bioengineering, biological, and clinical hurdles that now need to be addressed if the goals of life-long cure of hypothyroidism through cell- and/or gene-based therapies are to be attained. [ABSTRACT FROM AUTHOR]

The replacement of regenerated thyroid follicular cells (TFCs) is a promising therapeutic strategy for patients with hypothyroidism. Here, we have succeeded in inducing functional TFCs from human-induced pluripotent stem cells (iPSCs) in scalable suspension culture. Differentiation of iPSCs with Activin A treatment produced Sox17- and FoxA2-expressing definitive endodermal cells that also expressed thyroid transcription factors Pax8 and Nkx2-1. Further treatment with thyroid-stimulating hormone (TSH) induced TFCs expressing various types of thyroid proteins including TSH receptor, sodium–iodide symporter, thyroglobulin, and thyroid peroxidase. Interestingly, differentiated cells secreted free thyroxine in vitro. These results indicate successful differentiation of human iPSCs to functional TFCs that may enable us to fabricate thyroid tissues for regenerative medicine and disease models.