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

The adrenal glandis 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 adrenalcell model derived from fetal adrenalspecimens 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 organoidswith a structure similar to the fetal gland. The organoidsshow morphofunctional features and adrenalsteroidogenic factor, steroid acute regulatory, cyt...