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Functional anterior pituitary generated in self-organizing culture of human embryonic stem cells
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Functional anterior pituitary generated in self-organizing culture of human embryonic stem cells
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Journal Article
Functional anterior pituitary generated in self-organizing culture of human embryonic stem cells
2016
Overview
Anterior pituitary is critical for endocrine systems. Its hormonal responses to positive and negative regulators are indispensable for homeostasis. For this reason, generating human anterior pituitary tissue that retains regulatory hormonal control
in vitro
is an important step for the development of cell transplantation therapy for pituitary diseases. Here we achieve this by recapitulating mouse pituitary development using human embryonic stem cells. We find that anterior pituitary self-forms
in vitro
following the co-induction of hypothalamic and oral ectoderm. The juxtaposition of these tissues facilitated the formation of pituitary placode, which subsequently differentiated into pituitary hormone-producing cells. They responded normally to both releasing and feedback signals. In addition, after transplantation into hypopituitary mice, the
in vitro
-generated corticotrophs rescued physical activity levels and survival of the hosts. Thus, we report a useful methodology for the production of regulator-responsive human pituitary tissue that may benefit future studies in regenerative medicine.
It is difficult to generate functional human anterior pituitary tissues
in vitro
. Here, Ozone
et al.
generate human anterior pituitary from embryonic stem cells by recapitulating
in vivo
development, and demonstrate this tissue secretes hormones and rescues hypopituitarism when grafted into mice.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ Adrenocorticotropic Hormone - secretion
/ Animals
/ Corticotrophs - transplantation
/ Diabetes
/ Embryonic Stem Cells - physiology
/ Hormones
/ Humanities and Social Sciences
/ Humans
/ Kinases
/ Mice
/ Pituitary Gland, Anterior - embryology
/ Pituitary Gland, Anterior - secretion
/ Science
