DIFFERENTIATION OF HUMAN THYROID-FOLLICLE CELLS FROM NORMAL SUBJECTS AND BASEDOWS-DISEASE IN 3-DIMENSIONAL COLLAGEN GEL CULTURE

Thyroid follicles, an essential functional unit of the thyroid, exist in the extracellular matrix of the tissue in vivo. Therefore, in any monolayer culture system, the follicles cannot be reconstructed. Our previous study adopting three-dimensional collagen gel culture showed that isolated porcine follicle cells reconstructed thyroid follicles specific for the thyroid gland in vivo. To elucidate whether this culture system is also applicable to human follicle cells, and furthermore to provide a culture system for investigations of the pathogenesis of human thyroid diseases, we tried to culture isolated human follicle cells of normal thyroid tissue and of Basedow's disease in three-dimensional collagen gel. In this culture system, they apparently reconstructed thyroid follicles. The component cells of the reconstructed follicles exhibited structural polarity specific for human thyroid follicle cells and produced thyroid hormones. In addition, the cells responded to a TSH-stimulation in terms of morphological and functional differentiation, and they presented HLA-DR antigen with an interferon-gamma-stimulation. This report is a first instance of reconstruction of human thyroid follicles and HLA-DR antigen induction in three-dimensional follicle structures in vitro. This culture system provides a more physiological environment in vitro for biological and pathogenetic investigations of human thyroid follicle cells than the monolayer culture system. Further experiments using this method will probably provide new clues to the pathogenetic mechanisms of human thyroid diseases.