Generating 3D pituitary organoids from stem cells
Human pluripotent stem cells have been successfully converted into purified hormone-secreting pituitary tissue.
The pituitary gland plays an important role in hormone regulation and controlling different processes in the body, including metabolism, reproduction and growth. Decreased function of the pituitary gland leads to a condition known as hypopituitarism, which results in a deficiency of the hormones secreted by the gland. With no curative treatments available for the condition, a team of researchers from Nagoya University (Japan) sought to find out how regenerative medicine approaches could be utilized to develop a long-term cure.
The findings detail how the team created 3D pituitaries that had the capacity to secrete adrenocorticotropic hormone (ACTH). The team induced pituitary-hypothalamic tissue from human pluripotent stem cells (hPSCs), which were then purified with cell sorting utilizing a pituitary cell-surface marker to acquire a pituitary cell population. These purified pituitary cells aggregated to form 3D pituitaries that had the ability to secrete ACTH.
The researchers also assessed the response of the pituitary-hypothalamic tissue to positive and negative stimuli. Following treatment with corticotrophin-releasing hormone response (CRH) and glucocorticoid dexamethasone (DX), they found that there was a significant increase in ACTH secretion with CRH treatment and a decrease in ACTH secretion with the addition of DX.
In addition to the in vitro study conducted by the team, they also tested their findings in an in vivo model. The 3D pituitaries were transplanted into hypopituitary mice, where they were engrafted under the renal capsule. The transplanted 3D pituitaries survived for six months with an improvement in the blood ACTH levels observed by the team. Negative feedback by DX overrode stimulation by CRH in these mouse models, suggesting that this may potentially reduce the side effects of replacing ACTH.
The study was funded by several organizations including Japan Agency for Medical Research and Development, the Japan Science and Technology Agency and Nagoya University Hospital. The findings from the study mark a significant step forward in translational research, with the study suggesting that human pituitary tissue that is responsive to the surrounding environment could be generated from hPSCs and purified for clinical use for hypopituitarism.
Looking forward, Hidetaka Suka, one of the authors of the study stated:
“Our strategies open new avenues toward high-quality pituitary cell production suitable for pituitary regenerative medicine. For non-clinical or clinical studies, we will continue to develop manufacturing methods for clinical-grade cell lines, evaluate the efficacy of these lines in animals such as monkeys, and confirm the functionality of products after transplantation.”