Adrenocortical organoids: A promising tool for modelling human physiology and translational research

The adrenal cortex is a vital endocrine organ that controls a wide range of biological parameters including metabolism, blood pressure and immune response, through the release of distinct steroid hormones. As adrenal diseases can be life-threatening, understanding their molecular underpinnings and developing novel therapeutic approaches are important goals. Organoids have emerged as powerful research tools to study human fundamental biological processes, model diseases and develop novel therapies. However, research on adrenocortical organoids has only been reported recently, with a shift in focus from the use of immortalized cell lines to the emerging use of stem cells. Initially, forced expression of NR5A1 was used, but the field has evolved to prioritize directed differentiation. To date, few protocols have been reported that allow the directed differentiation of pluripotent stem cells into adrenocortical cells.This review provides the developmental background knowledge required for developing such cell systems, reports on the present state of the art and discusses how the implementation of in vitro organoid/spheroid cultures in the adrenal field can expand our basic understanding of tissue function and influence preclinical research.