Toda S, Yonemitsu N, Hikichi Y, Sugihara H, Koike N
Department of Pathology, Saga Medical School, Japan.
Pathol Res Pract. 1992 Oct;188(7):874-82. doi: 10.1016/s0344-0338(11)80247-5.
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.
甲状腺滤泡是甲状腺的基本功能单位,在体内存在于组织的细胞外基质中。因此,在任何单层培养系统中都无法重建滤泡。我们之前采用三维胶原凝胶培养的研究表明,分离的猪滤泡细胞在体内重建了甲状腺特有的甲状腺滤泡。为了阐明这种培养系统是否也适用于人滤泡细胞,进而为研究人类甲状腺疾病的发病机制提供一种培养系统,我们尝试在三维胶原凝胶中培养来自正常甲状腺组织和巴塞多氏病的分离人滤泡细胞。在这种培养系统中,它们明显重建了甲状腺滤泡。重建滤泡的组成细胞表现出人类甲状腺滤泡细胞特有的结构极性,并产生甲状腺激素。此外,这些细胞在形态和功能分化方面对促甲状腺激素刺激有反应,并且在γ干扰素刺激下呈现HLA - DR抗原。本报告首次在体外三维滤泡结构中重建了人类甲状腺滤泡并诱导了HLA - DR抗原。与单层培养系统相比,这种培养系统为人类甲状腺滤泡细胞的生物学和发病机制研究提供了更接近生理状态的体外环境。使用这种方法的进一步实验可能会为人类甲状腺疾病的发病机制提供新线索。