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Parathyroid-on-a-chip simulating parathyroid hormone secretion in response to calcium concentration
Lab on a Chip ( IF 6.1 ) Pub Date : 2024-05-27 , DOI: 10.1039/d4lc00249k
Sunghan Lee 1, 2 , Hyo-Il Jung 1, 3 , Jaehun Lee 1, 2 , Youngwon Kim 1, 2 , Jaewoo Chung 4 , Han Su Kim 5 , Jiseok Lim 6, 7 , Ki Chang Nam 2 , Yun-Sung Lim 8 , Han Seok Choi 9 , Bong Seop Kwak 2, 7
Affiliation  

The parathyroid gland is an endocrine organ that plays a crucial role in regulating calcium levels in blood serum through the secretion of parathyroid hormone (PTH). Hypoparathyroidism is a chronic disease that can occur due to parathyroid defects, but due to the difficulty of creating animal models of this disease or obtaining human normal parathyroid cells, the evaluation of parathyroid functionality for drug development is limited. Although parathyroid-like cells that secrete PTH have recently been reported, their functionality may be overestimated using traditional culture methods that lack in vivo similarities, particularly vascularization. To overcome these limitations, we obtained parathyroid organoids from tonsil-derived mesenchymal stem cells (TMSCs) and fabricated a parathyroid-on-a-chip, capable of simulating PTH secretion based on calcium concentration. This chip exhibited differences in PTH secretion according to calcium concentration and secreted PTH within the range of normal serum levels. In addition, branches of organoids, which are difficult to observe in animal models, were observed in this chip. This could serve as a guideline for successful engraftment in implantation therapies in the future.

中文翻译:


甲状旁腺芯片模拟甲状旁腺激素分泌对钙浓度的反应



甲状旁腺是一种内分泌器官,通过分泌甲状旁腺激素(PTH)在调节血清钙水平方面发挥着至关重要的作用。甲状旁腺功能减退症是一种因甲状旁腺缺陷而发生的慢性疾病,但由于难以创建该疾病的动物模型或获得人类正常甲状旁腺细胞,因此用于药物开发的甲状旁腺功能评估受到限制。尽管最近报道了分泌 PTH 的甲状旁腺样细胞,但使用缺乏体内相似性的传统培养方法(尤其是血管化)可能会高估其功能。为了克服这些限制,我们从扁桃体来源的间充质干细胞(TMSC)中获得了甲状旁腺类器官,并制造了甲状旁腺芯片,能够根据钙浓度模拟 PTH 分泌。该芯片根据钙浓度表现出 PTH 分泌差异,并在正常血清水平范围内分泌 PTH。此外,在该芯片中还观察到了在动物模型中难以观察到的类器官的分支。这可以作为未来植入治疗中成功植入的指南。
更新日期:2024-05-27
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