Thyrocyte integration, and thyroid folliculogenesis and tissue regeneration: perspective for thyroid tissue engineering.

The thyroid gland is composed of many ball-like structures called thyroid follicles, which are supported by the interfollicular extracellular matrix (ECM) and a capillary network. The component thyrocytes are highly integrated in their specific structural and functional polarization. In conventional monolayer and floating culture systems, thyrocytes cannot organize themselves into follicles with normal polarity. In contrast, in 3-D collagen gel culture, thyrocytes easily form stable follicles with physiological polarity. Integration of thyrocyte growth and differentiation results ultimately in thyroid folliculogenesis. This culture method and subacute thyroiditis are two promising models for addressing mechanisms of folliculogenesis, because thyroid-follicle formation actively occurs both in the culture system and at the regenerative phase of the disorder. The understanding of the mechanistic basis of folliculogenesis is prerequisite for generation of artificial thyroid tissue, which would enable a more physiological strategy to the treatment of hypothyroidism caused by various diseases and surgical processes than conventional hormone replacement therapy. We review here thyrocyte integration, and thyroid folliculogenesis and tissue regeneration. We also briefly discuss a perspective for thyroid tissue regeneration and engineering.