Recipe for pituitary organoids

Front Endocrinol (Lausanne). 2023 Jan 19:13:1025825. doi: 10.3389/fendo.2022.1025825. eCollection 2022.

Abstract

Generation of a variety of organs and tissues from human pluripotent stem cells (hPSCs) has been attempted in vitro. We here present a simple and efficient method for induction of hypothalamic and pituitary tissues from hPSCs. On provision of exogenous agents important for early hypothalamus-pituitary organogenesis, including bone morphogenetic protein 4 and activators of sonic hedgehog, in three-dimensional culture, hPSCs spontaneously form spherical organoids with two distinct tissues, hypothalamus and adenohypophysis. The pituitary tissues derived from hPSCs not only secrete adenocorticotropic hormone, but also retain both positive and negative feedback mechanisms, recapitulating mature endocrine organs in vivo. Furthermore, the results of ectopic transplantation with mouse models of hypopituitarism suggest that these hypothalamus-pituitary organoids have potential as engraftment organs. In addition to their use in transplantation for patients with hypopituitarism they will allow establishment of disease models in vitro and enable research impossible in humans. Hypothalamus-pituitary organoids promise to be a powerful tool in regenerative medicine, drug discovery, and basic research into pituitary development.

Keywords: corticotroph; embryonic stem cells; induced pluripotent stem cells; organoid; pituitary; pluripotent stem cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Hedgehog Proteins
  • Humans
  • Hypopituitarism*
  • Mice
  • Organoids*
  • Pituitary Gland*

Substances

  • Hedgehog Proteins

Grants and funding

This work was supported by grants from the Centers for Clinical Application Research on Specific Disease/Organ (to HSu) of the Research Center Network for Realization of Regenerative Medicine, funded by the Japan Agency for Medical Research and Development (AMED) under Grant Number JP21ek0109524; Grant-in-Aid for Scientific Research (to HSu), funded by the Japan Society for the Promotion of Science (JSPS) KAKENHI under Grant Number JP20K08859; Fusion Oriented REsearch for disruptive Science and Technology (FOREST) (to HSu), funded by Japan Science and Technology Agency (JST) under Grant Number JPMJFR200N; Grant-in-Aid for Early-Career Scientists (to MK), funded by JSPS KAKENHI under Grant Number JP21K16337; THE HORI SCIENCES AND ARTS FOUNDATION (to HSu); Takahashi Industrial and Economic Research Foundation (to HSu); Chukyo Longevity Medical and Promotion Foundation (to HSu); Harmonic Ito Foundation (to HSu); Ichihara International Scholarship Foundation (to HSu).