Stem Cells Derived from Goiters in Adults Form Spheres in Response to Intense Growth Stimulation and Require Thyrotropin for Differentiation into Thyrocytes

Abstract

Objective:This study aimed to analyze under which conditions quiescent stem cells derived from human goiters can be propagated to outgrow and whether these cells have retained the capacity to differentiate into thyroid cells.Design: Stem cells were isolated by fluorescence-activated cell sorting as a side population by the Hoechst 33342 efflux technique. Growth pattern of stem cells and cocultures of stem cells with thyrocytes grown as monolayer and in Matrigel was investigated. Expression of stem cell markers, endodermal markers, and thyroidspecific markers was analyzed by RT-PCR. In stem cell-derived thyrocytes, embedded in collagen to form follicles, TSH-dependent 125 iodide uptake was measured.Results: Stem cells were isolated as a side population from a non-side population fraction that consisted of endodermal marker-positive cells and thyroid cells. Intense growth stimulation of stem cells in coculture with thyrocytes resulted in formation of nonadherent, three-dimensional spheres that consisted of highly proliferating stem cells with their characteristic expression profiles. In response to TSH and serum, sphere-derived progenitor cells differentiated into thyrocytes that expressed paired box gene 8, thyroglobulin, sodium iodide symporter, thyroid-stimulating hormone receptor, and thyroperoxidase mRNA and showed TSH-dependent 125 iodide uptake. Conclusion

Thyroid stem cells: lessons from normal development and thyroid cancer

“…These findings reinforce the hypothesis that a subpopulation of pluripotent stem cells exists within goitrous thyroid (Thomas et al 2006, Hoshi et al 2007. Thyroid stem cells isolated from primary cultures derived from human goiters can differentiate into thyroid cells in vitro (Lan et al 2007). Stem cells were isolated from primary thyroid cultures and grown either as a monolayer or embedded in collagen.…”

“…Stem cells were isolated from primary thyroid cultures and grown either as a monolayer or embedded in collagen. Cells induced with TSH in serumenriched medium expressed Pax8, Tg, NIS, TSHR, and TPO mRNA (Lan et al 2007). Furthermore, differentiated cells embedded in collagen can take up iodide when stimulated with TSH (Lan et al 2007).…”

Normal vs cancer thyroid stem cells: the road to transformation

“…Moreover, when embedded in collagen, they were able to uptake iodine in response to TSH. 55 These results reinforce the reported observations regarding the ability of goitre-derived ASCs, to differentiate into thyroid cells.…”

Oestrogen action on thyroid progenitor cells: relevant for the pathogenesis of thyroid nodules?

“…These cells reside in all tissues and organs and are capable of proliferating during the lifetime of the organism (Levi & Morrison 2008). Stem cells have been identified in the human thyroid gland (Thomas et al 2006, Lan et al 2007, Fierabracci et al 2008 and cancer stem cells in thyroid cancer cells and tissues (Mitsutake et al 2007, Todaro et al 2010, Zheng et al 2010, Malaguarnera et al 2011. Orthotopic transplantation of stem cells derived from undifferentiated thyroid cancer tissues into a mouse thyroid gland recapitulated the nature and behaviour of the original tumour, which supported the concept of stem cells being the source of tumour formation (Todaro et al 2010, Derwahl 2011.…”

“…Human thyrocytes and primary thyrospheres isolated from nodular goitres of 58 patients after thyroidectomy were cultured as described by our group previously (Lan et al 2007). The mean age of the patients (40 females and 18 males) was 53.1G14.0 years.…”