Cell Population Kinetics in Dog and Human Adult Thyroid

Abstract

Cell population kinetics was studied by bromodeoxyuridine (BrdU) histochemical and 3H thymidine radioautographic labelling in dog thyroids. In-vivo labelling with BrdU and in-vitro labelling of incubated slices with 3H thymidine gave similar results. This validates the use of in-vitro labelling of slices for the study of cell kinetics in the thyroid. In-vitro labelling of human thyroid slices demonstrated a labelling index of 13.4 x 10(-5) for follicular cells; assuming an S phase of 10 h, this corresponds to a turnover time of the order of 8.5 years for the follicular cells. Stromal cells appear to turn over faster. These results show for the first time that human thyroid cells divide about five times during adulthood and therefore that the steady state level of thyroid cell mass results from a balance between cell division and cell loss. A shorter turnover time was found as expected in the thyroid of an adolescent and in follicular colloid nodules.

Relevance of iodine intake as a reputed predisposing factor for thyroid cancer

“…Certain unregulated growth signals associated with malignant transformation may contribute to the loss of differentiated thyroid function. The thyroid cell turns over, on average, no more than five times through adulthood (25). Turnover increases in early infancy and adolescence (25,26).…”

“…The thyroid cell turns over, on average, no more than five times through adulthood (25). Turnover increases in early infancy and adolescence (25,26). Because of the homogeneity of the growth potential of follicular cells (27), a fraction of these follicular cells in adults would likely turnover much more than five times.…”

Normal vs cancer thyroid stem cells: the road to transformation

“…8,16 It has been suggested that follicle regeneration is maintained by a pool of SCs that reside in the adult gland. ASCs, estimated to be~0.1% of all thyroid cells, are undifferentiated in a quiescent or slow-cycling state and could replicate themselves to Figure 2.…”

“…13,14 However, this model is not in accordance with the rare occurrence of RET/PTC and PAX8/PPARG rearrangements in ATC 15 and the low turnover rate of thyroid follicular cells (about five renewals per lifetime) that reduces the possibility of accumulating the mutations needed for transformation. 8,[16][17][18] The existence of several differentiation degrees has led to the assumption that TC cells are derived from remnants of fetal thyroid cells, such as stem cells (SCs) or precursors, rather than mature follicular cells. 9,19,20 According to this fetal cell carcinogenesis model supported by gene expression profiling data, ATC arises from fetal thyroid SCs, marked by the onco-fetal fibronectin expression and lack of differentiation markers.…”

Pathological processes and therapeutic advances in radioiodide refractory thyroid cancer

“…The thyroid gland is capable of regenerating itself, at least to some extent, which is thought to be facilitated by stem or progenitor cells present inside the adult gland located in a niche designated as solid cell nests (Coclet et al 1989, Gibelli et al 2009). Thyroid stem cells are characterized by the expression of p63, Oct-4, hNanog, CD44 and SCA-1 and are able to differentiate into fully functional thyroid follicular cells (Hoshi et al 2007, Lan et al 2007, Klonisch et al 2009, Ahn et al 2014.…”