Generating Functioning Pituitary Gland Organoids From Patient-Derived Induced Pluripotent Stem Cells (iPSCs)

Authors

• ML Ghermay
• AC Wcislak

Abstract

The vertebrate anterior pituitary gland is a ‘master’ hormone regulator with 5 distinct cell types and a highly organized architecture. Hypopituitarism, a deficiency in the hormones produced by the gland, can result from the currently available treatments for pituitary adenomas, such as chemotherapy, radiation, and surgery. Despite pituitary adenomas occurring in up to 30% of the general population, the current available models fail to recapitulate the gland's intricacies. We propose an optimized anterior pituitary corticotroph (APCor) paradigm free of highly oxidative stress and flow cytometry sorting. The goal of the APCor protocol is to develop patient-specific organoids from human induced pluripotent stem cells (hiPSCs) in order to model disease states and tumorigenesis, as well as establish a tissue therapy paradigm for patients with hypopituitarism. Immunocytochemistry images show temporal cell class development consistent with mature corticotroph fate. Stimulation with corticotrophin-releasing hormone (CRH) on mature cells at days 30 and 60 shows an increase in the release of adrenocorticotropic hormone (ACTH) as detected by ELISA. 3D cell culture, with and without the use of a decellularized matrix scaffold, shows similar results consistent with expected differentiation. Preliminary studies with hiPSCs reprogrammed from peripheral blood mononuclear cells (PBMCs) by Sendai virus show promising results for direction through the APCor protocol. In the future, this paradigm will be used for pre-clinical implantation of pituitary organoids in animal models of hypophysectomy.

Scientific Focus Area: Neuroscience

This page was last updated on Tuesday, August 6, 2024