Matsumoto Ryusaku, Suga Hidetaka, Arima Hiroshi, Yamamoto Takuya
Center for iPS Cell Research and Application, Kyoto University, Kyoto 606-8507, Japan.
Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
Cancers (Basel). 2022 Jul 27;14(15):3660. doi: 10.3390/cancers14153660.
Pituitary adenomas are characterized by abnormal growth in the pituitary gland. Surgical excision is the first-line treatment for functional (hormone-producing) pituitary adenomas, except for prolactin-producing adenomas; however, complete excision is technically challenging, and many patients require long-term medication after the treatment. In addition, the pathophysiology of pituitary adenomas, such as tumorigenesis, has not been fully understood. Pituitary adenoma pathophysiology has mainly been studied using animal models and animal tumor-derived cell lines. Nevertheless, experimental studies on human pituitary adenomas are difficult because of the significant differences among species and the lack of reliable cell lines. Recently, several methods have been established to differentiate pituitary cells from human pluripotent stem cells (hPSCs). The induced pituitary hormone-producing cells retain the physiological properties already lost in tumor-derived cell lines. Moreover, CRISPR/Cas9 systems have expedited the introduction of causative gene mutations in various malignant tumors into hPSCs. Therefore, hPSC-derived pituitary cells have great potential as a novel platform for studying the pathophysiology of human-specific pituitary adenomas and developing novel drugs. This review presents an overview of the recent progresses in hPSC applications for pituitary research, functional pituitary adenoma pathogenesis, and genome-editing techniques for introducing causative mutations. We also discuss future applications of hPSCs for studying pituitary adenomas.
垂体腺瘤的特征是垂体异常生长。手术切除是功能性（产生激素的）垂体腺瘤的一线治疗方法，但泌乳素分泌型腺瘤除外；然而，完全切除在技术上具有挑战性，许多患者在治疗后需要长期服药。此外，垂体腺瘤的病理生理学，如肿瘤发生，尚未完全了解。垂体腺瘤的病理生理学主要通过动物模型和动物肿瘤衍生细胞系进行研究。然而，由于物种间的显著差异和缺乏可靠的细胞系，对人类垂体腺瘤的实验研究很困难。最近，已经建立了几种从人多能干细胞（hPSC）中分化垂体细胞的方法。诱导产生垂体激素的细胞保留了肿瘤衍生细胞系中已经丧失的生理特性。此外，CRISPR/Cas9系统加快了将各种恶性肿瘤中的致病基因突变引入hPSC的速度。因此，hPSC衍生的垂体细胞作为研究人类特异性垂体腺瘤病理生理学和开发新药的新型平台具有巨大潜力。本综述概述了hPSC在垂体研究、功能性垂体腺瘤发病机制以及引入致病突变的基因组编辑技术方面的最新进展。我们还讨论了hPSC在垂体腺瘤研究中的未来应用。
