Thyrocyte integration, and thyroid folliculogenesis and tissue regeneration: Perspective for thyroid tissue engineering

Abstract

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.

Thyrocytes, but not C cells, actively undergo growth and folliculogenesis at the periphery of thyroid tissue fragments in three-dimensional collagen gel culture

“…Thyrocytes within the follicles concentrated in the central zone may be subjected to a growth-inhibitory mechanism such as contact inhibition of cell growth, whereas thyrocytes within the follicles dispersed in the peripheral part may escape from such inhibitory regulation. As this issue is crucial for thyroid tissue regeneration or engineering (Toda et al 2001), further studies are in order. In addition, our study demonstrated that neogenic follicles rarely had C cells; and that C cells showed no proliferative ability.…”

Culture system for studying thyroid biology

“…To investigate thyroid biology, monolayer and floating culture systems have been developed and widely used [2][3][4][5]. These methods have facilitated thyroid biology.…”

“…These methods have facilitated thyroid biology. However, the conventional methods, in which thyrocytes are unable to organize follicle structures, cannot satisfactorily provide thyrocytes with normal cellular integration [2][3][4][5]. In contrast, three-dimensional (3-D) collagen gel culture system allows thyrocytes to achieve follicle structures with their physiological polarity.…”

“…In contrast, three-dimensional (3-D) collagen gel culture system allows thyrocytes to achieve follicle structures with their physiological polarity. This method is thus suitable for studying the biological behavior of thyrocytes in a microenvironment which more closely simulates physiological conditions [4,5]. These culture systems cannot, however, reconstruct follicle structures that consist of both thyrocytes and C cells.…”

“…Monolayer and floating culture systems [2][3][4][5] Thyrocyte monolayer culture initiated by Pulvertaft in 1956 [2] has been used for studying proliferation and differentiation of thyrocytes. However, monolayer culture cannot satisfactorily enable thyrocytes to achieve normal structural and functional polarities.…”