Benchmark for Setting ACTH Cell Dosage in Clinical Regenerative Medicine for Post-Operative Hypopituitarism.

IF 2.9 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Diseases (Basel, Switzerland) Pub Date : 2025-04-10 DOI:10.3390/diseases13040112

Tatsuma Kondo, Hidetaka Suga, Kazuhito Takeuchi, Yutaro Fuse, Yoshiki Sato, Toshiaki Hirose, Harada Hideyuki, Yuichi Nagata, Ryuta Saito

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Abstract

Background/objectives: Our objective is to develop hormone-producing pituitary cells that can function in the same manner as the human body and provide more effective treatments than current hormone replacement therapy. We have already established a technique for generating hypothalamic-pituitary organoids using feeder-free human pluripotent stem cells (hPSCs) and demonstrated their effectiveness in vivo through transplantation into hypopituitary mouse models. To prospectively determine the upper limit of transplanting adenohypophyseal cells into humans, we investigated the human maximum secretion capacity of adrenocorticotropic hormone (ACTH) and growth hormone (GH).

Methods: We analyzed data from 28 patients with pituitary adenomas, among whom 16 evinced no abnormality of ACTH secretion and 12 showed no GH secretion on corticotropin-releasing hormone (CRH) and growth hormone-releasing hormone-2 (GHRP-2) stimulation testing.

Results: The average ACTH peak value after CRH stimulation tests was 97.2 pg/mL, and the average GH peak value after GHRP-2 stimulation tests was 25.1 ng/mL.

Conclusions: These data will likely serve as benchmarks of ACTH and GH secretion when transplanting cultured cells into humans.

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术后垂体功能减退临床再生医学中ACTH细胞剂量设定的基准。

背景/目的：我们的目标是开发能产生激素的垂体细胞，使其能以与人体相同的方式发挥作用，并提供比目前的激素替代疗法更有效的治疗方法。我们已经建立了一种使用无喂食的人类多能干细胞（hPSCs）产生下丘脑-垂体类器官的技术，并通过移植到下丘脑-垂体小鼠模型中证明了其在体内的有效性。为了前瞻性地确定腺垂体细胞移植到人体内的上限，我们研究了人促肾上腺皮质激素（ACTH）和生长激素（GH）的最大分泌能力。方法：对28例垂体腺瘤患者资料进行分析，其中促肾上腺皮质激素释放激素（CRH）和生长激素释放激素-2 （GHRP-2）刺激试验显示，促肾上腺皮质激素释放激素（ACTH）分泌无异常16例，促肾上腺皮质激素释放激素-2 （GHRP-2）刺激试验显示无GH分泌12例。结果：CRH刺激后ACTH平均峰值为97.2 pg/mL， GHRP-2刺激后GH平均峰值为25.1 ng/mL。结论：这些数据可能作为将培养细胞移植到人体内时ACTH和GH分泌的基准。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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