MONDAY, Nov. 14 (HealthDay News) -- A functional pituitary gland can be produced from mouse embryonic stem cells, opening the door to possible new therapies for diseases of the pituitary gland, according to an experimental study published online Nov. 9 in Nature.
Hidetaka Suga, from the RIKEN Center for Developmental Biology in Kobe, Japan, and colleagues investigated how Rathke's pouch is induced in the embryonic head ectoderm. Mouse embryonic stem cells were cultured into an aggregate for maintenance and differentiation. An inverted confocal microscope combined with oxygen and carbon dioxide incubators enabled long-term live imaging of the three-dimensional culture. Aggregates were analyzed in vitro to investigate adrenocorticotropic hormone release. In vivo testing involved injection of aggregates into hypopituitary mice.
The investigators found that three-dimensional adenohypophysis tissues self-form into an aggregate culture of mouse embryonic cells. Within the aggregate, the embryonic stem cells differentiated into non-neural head ectoderm and hypothalamic neuroectoderm in adjacent layers. In vivo studies demonstrated that, at the interface of these two epithelia, there was self-organization of Rathke's-pouch-like three-dimensional structures. Subsequently, various endocrine cells such as corticotrophs and somatotrophs were produced. In response to corticotrophin-releasing hormone, the corticotrophs secreted adrenocorticotropic hormone. When these cells were grafted in vivo, they rescued the systemic glucocorticoid level in hypopituitary mice.
"Using a synthetic approach at the multi-cellular level, we demonstrated that a functional organ bud, the development of which requires intricate tissue interactions, can be reproducibly generated by self-formation when the spatial arrangement of a few interacting tissues is reconstituted in three-dimensional culture," the authors write.
Abstract
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