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Self-formation of functional adenohypophysis in three-dimensional culture
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Journal Article
Self-formation of functional adenohypophysis in three-dimensional culture
2011
Overview
The adenohypophysis (anterior pituitary) is a major centre for systemic hormones. At present, no efficient stem-cell culture for its generation is available, partly because of insufficient knowledge about how the pituitary primordium (Rathke’s pouch) is induced in the embryonic head ectoderm. Here we report efficient self-formation of three-dimensional adenohypophysis tissues in an aggregate culture of mouse embryonic stem (ES) cells. ES cells were stimulated to differentiate into non-neural head ectoderm and hypothalamic neuroectoderm in adjacent layers within the aggregate, and treated with hedgehog signalling. Self-organization of Rathke’s-pouch-like three-dimensional structures occurred at the interface of these two epithelia, as seen
in vivo
, and various endocrine cells including corticotrophs and somatotrophs were subsequently produced. The corticotrophs efficiently secreted adrenocorticotropic hormone in response to corticotrophin releasing hormone and, when grafted
in vivo
, these cells rescued the systemic glucocorticoid level in hypopituitary mice. Thus, functional anterior pituitary tissue self-forms in ES cell culture, recapitulating local tissue interactions.
Mouse embryonic stem cells are induced to form functional anterior pituitary tissue in three-dimensional culture.
Pituitary tissue grown from stem cells
A three-dimensional cell culture system has been developed that produces functioning pituitary tissue from mouse embryonic stem cells. The cells differentiate into layered structures, the development of which depends on close juxtaposition of two tissue types in formations that resemble local tissue reactions seen
in vivo
. Endocrine cells including corticotrophs and somatotrophs are produced. The corticotrophs efficiently secreted adrenocorticotropic hormone in response to corticotrophin releasing hormone, and transplantation of the pituitary tissues into a hypopituitary mouse model rescued a lethal deficiency in adrenocorticotropin. This work opens the possibility of developing regenerative therapies for pituitary defects, a major category of endocrinological disorders that includes empty sella syndrome, Sheehan syndrome and pituitary apoplexy.
Publisher
Nature Publishing Group UK,Nature Publishing Group
