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Induction of Functional Hypothalamus and Pituitary Tissues From Pluripotent Stem Cells for Regenerative Medicine

The hypothalamus and pituitary have been identified to play essential roles in maintaining homeostasis. Various diseases can disrupt the functions of these systems, which can often result in serious lifelong symptoms. The current treatment for hypopituitarism involves hormone replacement therapy. Ho...

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Autores principales: Kano, Mayuko, Suga, Hidetaka, Arima, Hiroshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880040/
https://www.ncbi.nlm.nih.gov/pubmed/33604493
http://dx.doi.org/10.1210/jendso/bvaa188
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author Kano, Mayuko
Suga, Hidetaka
Arima, Hiroshi
author_facet Kano, Mayuko
Suga, Hidetaka
Arima, Hiroshi
author_sort Kano, Mayuko
collection PubMed
description The hypothalamus and pituitary have been identified to play essential roles in maintaining homeostasis. Various diseases can disrupt the functions of these systems, which can often result in serious lifelong symptoms. The current treatment for hypopituitarism involves hormone replacement therapy. However, exogenous drug administration cannot mimic the physiological changes that are a result of hormone requirements. Therefore, patients are at a high risk of severe hormone deficiency, including adrenal crisis. Pluripotent stem cells (PSCs) self-proliferate and differentiate into all types of cells. The generation of endocrine tissues from PSCs has been considered as another new treatment for hypopituitarism. Our colleagues established a 3-dimensional (3D) culture method for embryonic stem cells (ESCs). In this culture, the ESC-derived aggregates exhibit self-organization and spontaneous formation of highly ordered patterning. Recent results have shown that strict removal of exogenous patterning factors during early differentiation efficiently induces rostral hypothalamic progenitors from mouse ESCs. These hypothalamic progenitors generate vasopressinergic neurons, which release neuropeptides upon exogenous stimulation. Subsequently, we reported adenohypophysis tissue self-formation in 3D cultures of mouse ESCs. The ESCs were found to differentiate into both nonneural oral ectoderm and hypothalamic neuroectoderm in adjacent layers. Interactions between the 2 tissues appear to be critically important for in vitro induction of a Rathke’s pouch-like developing embryo. Various endocrine cells were differentiated from nonneural ectoderm. The induced corticotrophs efficiently secreted adrenocorticotropic hormone when engrafted in vivo, which rescued hypopituitary hosts. For future regenerative medicine, generation of hypothalamic and pituitary tissues from human PSCs is necessary. We and other groups succeeded in establishing a differentiation method with the use of human PSCs. Researchers could use these methods for models of human diseases to elucidate disease pathology or screen potential therapeutics.
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spelling pubmed-78800402021-02-17 Induction of Functional Hypothalamus and Pituitary Tissues From Pluripotent Stem Cells for Regenerative Medicine Kano, Mayuko Suga, Hidetaka Arima, Hiroshi J Endocr Soc Mini-Reviews The hypothalamus and pituitary have been identified to play essential roles in maintaining homeostasis. Various diseases can disrupt the functions of these systems, which can often result in serious lifelong symptoms. The current treatment for hypopituitarism involves hormone replacement therapy. However, exogenous drug administration cannot mimic the physiological changes that are a result of hormone requirements. Therefore, patients are at a high risk of severe hormone deficiency, including adrenal crisis. Pluripotent stem cells (PSCs) self-proliferate and differentiate into all types of cells. The generation of endocrine tissues from PSCs has been considered as another new treatment for hypopituitarism. Our colleagues established a 3-dimensional (3D) culture method for embryonic stem cells (ESCs). In this culture, the ESC-derived aggregates exhibit self-organization and spontaneous formation of highly ordered patterning. Recent results have shown that strict removal of exogenous patterning factors during early differentiation efficiently induces rostral hypothalamic progenitors from mouse ESCs. These hypothalamic progenitors generate vasopressinergic neurons, which release neuropeptides upon exogenous stimulation. Subsequently, we reported adenohypophysis tissue self-formation in 3D cultures of mouse ESCs. The ESCs were found to differentiate into both nonneural oral ectoderm and hypothalamic neuroectoderm in adjacent layers. Interactions between the 2 tissues appear to be critically important for in vitro induction of a Rathke’s pouch-like developing embryo. Various endocrine cells were differentiated from nonneural ectoderm. The induced corticotrophs efficiently secreted adrenocorticotropic hormone when engrafted in vivo, which rescued hypopituitary hosts. For future regenerative medicine, generation of hypothalamic and pituitary tissues from human PSCs is necessary. We and other groups succeeded in establishing a differentiation method with the use of human PSCs. Researchers could use these methods for models of human diseases to elucidate disease pathology or screen potential therapeutics. Oxford University Press 2020-12-02 /pmc/articles/PMC7880040/ /pubmed/33604493 http://dx.doi.org/10.1210/jendso/bvaa188 Text en © The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Mini-Reviews
Kano, Mayuko
Suga, Hidetaka
Arima, Hiroshi
Induction of Functional Hypothalamus and Pituitary Tissues From Pluripotent Stem Cells for Regenerative Medicine
title Induction of Functional Hypothalamus and Pituitary Tissues From Pluripotent Stem Cells for Regenerative Medicine
title_full Induction of Functional Hypothalamus and Pituitary Tissues From Pluripotent Stem Cells for Regenerative Medicine
title_fullStr Induction of Functional Hypothalamus and Pituitary Tissues From Pluripotent Stem Cells for Regenerative Medicine
title_full_unstemmed Induction of Functional Hypothalamus and Pituitary Tissues From Pluripotent Stem Cells for Regenerative Medicine
title_short Induction of Functional Hypothalamus and Pituitary Tissues From Pluripotent Stem Cells for Regenerative Medicine
title_sort induction of functional hypothalamus and pituitary tissues from pluripotent stem cells for regenerative medicine
topic Mini-Reviews
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880040/
https://www.ncbi.nlm.nih.gov/pubmed/33604493
http://dx.doi.org/10.1210/jendso/bvaa188
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