All isoprenoids are synthesised from two simple precursors isopentenyl pyrophosphate

Thus, the origin and procedure of isolation of thyroid stem cells still remain obscure. Recent TACA reports have provided another clue to gain insight into source of primitive stem/progenitor cells. In 2007, induced pluripotent stem cells were established from adult human fibroblasts by direct reprogramming with defined factors. Recently, not only reprogramming but also generating tissue stem/progenitor cells has also been reported. Mani et al. have demonstrated that differentiated mammary epithelial cells can be converted into mammary tissue stem cells by introducing genes related to epithelial-mesenchymal transition. Moreover, cancer stem cells have also been generated from cancer cells or even from normal epithelial cells. These reports suggest that tissue stem/ progenitor cells could be generated from mature and differentiated cells. In the present study, we present a novel culture system in which progenitor cells can be emerged and propagated from normal human thyroid follicular cells by dedifferentiation. We also demonstrate that the cells possess multilineage Tramiprosate differentiation potential. In the present study, we have developed a novel system to trigger dedifferentiation of normal human thyroid follicular cells. We used a commercially available medium which allowed universal and reproducible procedure. We investigated the origin of the cells by analyzing expressions of STRO-1 and two intermediate filaments, cytokeratin-18 and vimentin. In our system, there were only two types of attached cells in terms of expression pattern of the above-mentioned markers after initial plating: cytokeratin-18/vimentin double-positive cells and STRO- 1/vimentin double-positive cells. Thyroid follicular cells coexpress cytokeratin-18 and vimentin, which is consistent with earlier studies. Cytokeratin-18/vimentin-positive cells may also contain a small number of endothelial cells since several papers demonstrated expression of cytokeratin in microvascular endothelial cells in different tissues. Although both cytokeratin-18 and vimentin expressions were observed even in undifferentiated thyroid cancer cell lines, the cytokeratin-18 expression was lost in the SAGM-grown cells. All of thyroid-specific gene expressions were not observed in the cells. Moreover, the SAGM-grown cells displayed high plasticity: multilineage differentiation potential into thyrocytes, neuronal cells and adipocytes. These results suggest that we have successfully dedifferentiated/converted thyroid follicular cells into multilineage progenitor cells. However, re-differentiation effects were modest compared to PT. We are currently seeking the better method enabling more efficient differentiation.

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