人胎儿肾上腺细胞在培养中保留与年龄相关的干细胞和内分泌分化潜能。

Human fetal adrenal cells retain age-related stem- and endocrine-differentiation potential in culture.

机构信息

Endocrinology Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy.

Histology and Embryology Unit, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.

出版信息

FASEB J. 2019 Feb;33(2):2263-2277. doi: 10.1096/fj.201801028RR. Epub 2018 Sep 24.

DOI:10.1096/fj.201801028RR

PMID:30247985

Abstract

The adrenal gland is a multiendocrine organ with a steroidogenic mesenchymal cortex and an inner catecholamine-producing medulla of neuroendocrine origin. After embryonic development, this plastic organ undergoes a functional postnatal remodeling. Elucidating these complex processes is pivotal for understanding the early bases of functional endocrine disorders and tumors affecting the mature gland. We developed an in vitro human adrenal cell model derived from fetal adrenal specimens at different gestational ages, consisting of neuroendocrine and cortical components and expressing the zona and functional markers of the original fetal organ. These cortical and neuroendocrine progenitor cells retain in vitro an intrinsic gestational-age-related differentiation and functional program. In vitro these cells spontaneously form 3-dimensional structure organoids with a structure similar to the fetal gland. The organoids show morphofunctional features and adrenal steroidogenic factor, steroid acute regulatory, cytochrome-P450-17A1, dosage-sensitive, sex-reversal, adrenal hypoplasia-critical region on chromosome X protein , NOTCH1, and nephroblastoma overexpressed/cysteine-rich protein 61/connective tissue growth factor/nephroblastoma overexpressed gene-3; stem (BMI1, nestin); and chromaffin (chromogranin A, tyrosine hydroxylase) markers similar to those of the populations of origin. This in vitro human adrenal system represents a unique but preliminar model for investigating the pathophysiological processes underlying physiologic adrenal remodeling and pathologic alterations involved in organ hypo- and hyperplasia and cancer.-Poli, G., Sarchielli, E., Guasti, D., Benvenuti, S., Ballerini, L., Mazzanti, B., Armignacco, R., Cantini, G., Lulli, M., Chortis, V., Arlt, W., Romagnoli, P., Vannelli, G. B., Mannelli, M., Luconi, M. Human fetal adrenal cells retain age-related stem- and endocrine-differentiation potential in culture.

摘要

肾上腺是一种具有类固醇生成间充质皮质和神经内分泌起源的儿茶酚胺产生髓质的多内分泌器官。在胚胎发育后，这个具有可塑性的器官会经历功能上的产后重塑。阐明这些复杂的过程对于理解影响成熟腺体的早期功能性内分泌紊乱和肿瘤的基础至关重要。我们开发了一种体外人肾上腺细胞模型，该模型源自不同胎龄的胎儿肾上腺标本，由神经内分泌和皮质成分组成，并表达原始胎儿器官的区带和功能标志物。这些皮质和神经内分泌祖细胞在体外保留了与胎龄相关的内在分化和功能程序。在体外，这些细胞自发形成具有类似于胎儿腺体的结构的 3 维结构类器官。类器官表现出形态功能特征和肾上腺甾体生成因子、甾体急性调节蛋白、细胞色素 P450-17A1、剂量敏感、性别反转、X 染色体肾上腺发育不全关键区蛋白、NOTCH1、肾母细胞瘤过表达/富含半胱氨酸蛋白 61/结缔组织生长因子/肾母细胞瘤过表达基因-3；干细胞（BMI1、巢蛋白）；和嗜铬细胞（嗜铬粒蛋白 A、酪氨酸羟化酶）标志物，类似于其来源的细胞群体。这种体外人肾上腺系统代表了一种独特但初步的模型，用于研究生理肾上腺重塑和参与器官发育不良和增生以及癌症的病理改变的生理病理过程。-Poli，G.，Sarchielli，E.，Guasti，D.，Benvenuti，S.，Ballerini，L.，Mazzanti，B.，Armignacco，R.，Cantini，G.，Lulli，M.，Chortis，V.，Arlt，W.，Romagnoli，P.，Vannelli，G. B.，Mannelli，M.，Luconi，M. 人胎儿肾上腺细胞在培养中保留与年龄相关的干细胞和内分泌分化潜能。