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    Induced Pluripotent Stem Cell-Derived Parathyroid Organoids Resemble Parathyroid Morphology and Function
    (Wiley, 2024) Senkal-Turhan, Selinay; Bulut-Okumus, Ezgi; Aydin, Muhterem; Turkmen, Nese Basak; Taslidere, Asli; Sahin, Fikrettin; Yilmaz, Sahin
    The primary role of the parathyroid glands is to maintain calcium homeostasis through the secretion of parathyroid hormone (PTH). The limited proliferative capacity and differentiation of parathyroid cells hinder the generation of cell therapy options. In this study, parathyroid organoids are successfully generated from human-induced pluripotent stem cells (hiPSCs). At the end of the 20 days of differentiation, the parathyroid organoids exhibited distinct parathyroid morphology. Stereomicroscope, scanning electron microscopy (SEM), and transmission electron microscopy (TEM) analysis demonstrated the 3D arrangement of the cell layers in which intracellular structures of parathyroid cells resemble human parathyroid cellular morphology. Comprehensive molecular analyses, including RNA sequencing (RNA-Seq) and liquid chromatography/mass spectrometry (LC-MS/MS), confirmed the expression of key parathyroid-related markers. Protein expression of CasR, CxCr4, Gcm2, and PTH are observed in parathyroid organoids. Parathyroid organoids secrete PTH, demonstrate active intercellular calcium signaling, and induce osteogenic differentiation via their secretome. The tissue integration potential of parathyroid organoids is determined by transplantation into parathyroidectomized rats. The organoid transplanted animals showed significant elevations in PTH-related markers (CasR, CxCr4, Foxn1, Gcm2, and PTH). PTH secretion is detected in organoid-transplanted animals. The findings represent a significant advancement in parathyroid organoid culture and may offer a cellular therapy for treating PTH-related diseases, including hypoparathyroidism. iPSC-derived parathyroid organoids express PTH-related markers at the protein and gene levels. The transplantation of parathyroid organoids into parathyroidectomized rats shows their functional activity and tissue integration capability. iPSC-derived parathyroid organoids successfully release PTH both in vitro and in vivo. Parathyroid organoid technology may improve defective parathyroid function and related diseases. image
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    The active plant compounds demonstrated positive activity on mouse intestinal organoids as an inflammation model system
    (Springer, 2026) Senkal-Turhan, Selinay; Boke, Ozum Begum; Bulut-Okumus, Ezgi; Soydan, Hazar Eren; Turkmen, Nese Basak; Senol, Ayca; Kadayifci, Kaan
    Diet has an important impact on intestinal homeostasis, and the establishment of appropriate experimental models to study the effect of food compounds is of interest. The organoid model can be used to check the positive protective role of active food compounds on intestinal tissue. In the current study, mouse intestinal organoids were used to model air-liquid interface (ALI), lipopolysaccharide (LPS)-induced inflammation, and macrophage co-culture-based inflammation modelling. The activity of hesperidin, capsaicin, allicin, and 18 beta-glycyrrhetinic acid (18 beta-GA) was determined in organoid culture. Morphology, crypt number, area, and intensity were analyzed. mRNA expression analysis and immunostaining analysis were performed for inflammation and proliferation markers. The ALI model exerted a suitable organoid culture system to mimic intestinal growth based on our results. Hesperidin, capsaicin, and allicin demonstrated positive effects on LPS-induced inflammation. All of the food compounds showed positive effects in macrophage co-culture for organoid structure and growth but not for macrophage proliferation and viability. All compounds reduced the inflammatory gene expression and increased stem cell marker and proliferation-related gene expression in the ALI model. In addition, capsaicin showed positive effects on organoid growth and maturation. This study generated an experimental model system to test food components and might be used in further research.