Thyroid Regeneration: Characterization of Clear Cells After Partial Thyroidectomy

Abstract

Although having the capacity to grow in response to a stimulus that perturbs the pituitary-thyroid axis, the thyroid gland is considered not a regenerative organ. In this study, partial thyroidectomy (PTx) was used to produce a condition for thyroid regeneration. In the intact thyroid gland, the central areas of both lobes served as the proliferative centers where microfollicles, and bromodeoxyuridine (BrdU)-positive and/or C cells, were localized. Two weeks after PTx, the number of BrdU-positive cells and cells with clear or faintly eosinophilic cytoplasm were markedly increased in the central area and continuous to the cut edge. Clear cells were scant in the cytoplasm, as determined by electron microscopy; some retained the characteristics of calcitonin-producing C cells by having neuroendocrine granules, whereas others retained follicular cell-specific features, such as the juxtaposition to a lumen with microvilli. Some cells were BrdU-positive and expressed Foxa2, the definitive endoderm lineage marker. Serum TSH levels drastically changed due to the thyroidectomy-induced acute reduction in T(4)-generating tissue, resulting in a goitrogenesis setting. Microarray followed by pathway analysis revealed that the expression of genes involved in embryonic development and cancer was affected by PTx. The results suggest that both C cells and follicular cells may be altered by PTx to become immature cells or immature cells that might be derived from stem/progenitor cells on their way to differentiation into C cells or follicular cells. These immature clear cells may participate in the repair and/or regeneration of the thyroid gland.

Regenerative Capacity of the Adult Pituitary: Multiple Mechanisms of Lactotrope Restoration After Transgenic Ablation

“…Possibly, no full restoration is needed to attain satisfactory hormone functions, or the mature organ, in contrast to the embryonic tissue, is not competent anymore for full restoration, as also found in other organs (see eg, [32][33][34]). In analogy, also other mature organs (e.g., thyroid gland, heart) only rarely regenerate to a full extent [8,35,36].…”

An Adult Mouse Thyroid Side Population Cell Line that Exhibits Enriched Epithelial–Mesenchymal Transition

“…For the latter, it was previously demonstrated that partial thyroidectomy can be used as a model for thyroid regeneration (15). When SPTL cells were orthotopically injected into the thyroid, many GFP-positive cells were found outside as well as inside the thyroid (Supplementary Fig.…”

“…Thyroid SP cells highly express genes involved in cancer and/or cancer invasion/ metastasis, as determined by microarray analysis, compared with non-SP cells, suggesting that thyroid SP cells may contain cancer stem cells of the thyroid (14). Further, partial thyroidectomy was established as a model for studying thyroid regeneration (15). In the partial thyroidectomized thyroid, many clear cells due to scantiness of the cytoplasm, indicative of immature cells, were observed that have characteristics of either C cells or follicular cells.…”

“…In the partial thyroidectomized thyroid, many clear cells due to scantiness of the cytoplasm, indicative of immature cells, were observed that have characteristics of either C cells or follicular cells. It was suggested that these immature cells may participate in the repair and/or regeneration of the thyroid gland (15). The formation of clear cells was considered as one of the pathways for thyroid regeneration (16).…”

Normal vs cancer thyroid stem cells: the road to transformation

“…52 They evolve into functional follicles, which express TPO after 120 days, indicating that they consist of newly formed follicular cells, but do not originate from differentiated thyrocytes. 51,52 Considering the SCN as a source for both follicular and C cells, the presence of three cell types has been hypothesised: (i) progenitors of follicular cells, arisen from the base of the foregut (endodermal origin); (ii) progenitors of C cells, which originate from ultimobranchial bodies (neural crest origin); and (iii) and the follicular and C bipotential progenitor cells. 8 In 1992, Dumont et al 17 first hypothesised the existence of ASCs within the mature thyroid gland.…”