Differentiation of thyroid cells to parathyroid cells in coculture environment

Parathyroid (Pt) is the only organ responsible for the secretion and release of parathormone (PTH), which regulates calcium and phosphorus homeostasis. Many essential physiological reactions in the body depend on the maintenance of this homeostasis. Imbalance in serum calcium causes many metabolic problems. Hypoparathyroidism is a condition characterized by low serum PTH, low calcium and high phosphate levels. The classical treatment of hypoparathyroidism consists of calcium and vitamin D supplementation. Recombinant human PTH preparations can also be used, but they are mostly not preferred because of their high cost. The most effective and permanent treatment option is parathyroid allo-transplantation (Pt allo-tx). The biggest problem in Pt allo-tx is finding a suitable donor and immune rejection. Various tissue engineering studies are carried out to overcome these problems, but still the problem has not been solved completely. In this study, it was aimed to create Pt organoid from stem cells of thyroid tissue, which has the same embryological origin as the parathyroid, in a coculture (COC) environment. Activin A and sonic hedgehog (Shh) were used as differentiation factors. After 14 days of incubation, differentiation was evaluated by gene expression profile analysis, biochemical PTH secretion measurement, and immunohistochemical (IHC) assessment. The actual measured PTH release values ​​of the formed COC organoids were higher than the expected PTH release values, and statistically significant increases in PTH release were observed between day 2 and day 14. By qPCR analysis, Pt specific PTH and CaSR gene expressions of the COC organoids were examined and increase in PTH (between 4.0 and 8.8 fold) and CaSR (between 1.2 and 28.2 fold) gene expressions were observed in all COC groups. Successful differentiation of thyroid stem cells into Pt-like cells in coculture can be speculated to microenvironmental factors such as interaction of cells of the same embryological origin, exosomes, etc. Our results are promising in terms of solving the immune rejection problem together with the donor limitation in case of allogenous parathyroid transplantation.