1. Derivation of Diverse Hormone-Releasing Pituitary Cells from Human Pluripotent Stem Cells.
- Author
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Zimmer B, Piao J, Ramnarine K, Tomishima MJ, Tabar V, and Studer L
- Subjects
- Adrenocorticotropic Hormone biosynthesis, Adrenocorticotropic Hormone metabolism, Animals, Benzamides pharmacology, Biomarkers metabolism, Bone Morphogenetic Protein 4 pharmacology, Cell Culture Techniques, Cell Differentiation drug effects, Cell- and Tissue-Based Therapy, Corticotrophs cytology, Corticotrophs drug effects, Dioxoles pharmacology, Disease Models, Animal, Embryonic Stem Cells cytology, Embryonic Stem Cells drug effects, Fibroblast Growth Factors pharmacology, Follicle Stimulating Hormone biosynthesis, Follicle Stimulating Hormone metabolism, GATA3 Transcription Factor genetics, GATA3 Transcription Factor metabolism, Gene Expression, Growth Hormone biosynthesis, Growth Hormone metabolism, Homeodomain Proteins genetics, Homeodomain Proteins metabolism, Humans, Hypopituitarism genetics, Hypopituitarism metabolism, Hypopituitarism pathology, Intracellular Signaling Peptides and Proteins genetics, Intracellular Signaling Peptides and Proteins metabolism, Mice, Nuclear Proteins genetics, Nuclear Proteins metabolism, Pituitary Gland metabolism, Pituitary Gland pathology, Pluripotent Stem Cells cytology, Pluripotent Stem Cells drug effects, Protein Tyrosine Phosphatases genetics, Protein Tyrosine Phosphatases metabolism, Thyrotrophs cytology, Thyrotrophs drug effects, Transcription Factor AP-2 genetics, Transcription Factor AP-2 metabolism, Transcription Factors genetics, Transcription Factors metabolism, Corticotrophs metabolism, Embryonic Stem Cells metabolism, Hypopituitarism therapy, Pluripotent Stem Cells metabolism, Thyrotrophs metabolism
- Abstract
Human pluripotent stem cells (hPSCs) provide an unlimited cell source for regenerative medicine. Hormone-producing cells are particularly suitable for cell therapy, and hypopituitarism, a defect in pituitary gland function, represents a promising therapeutic target. Previous studies have derived pituitary lineages from mouse and human ESCs using 3D organoid cultures that mimic the complex events underlying pituitary gland development in vivo. Instead of relying on unknown cellular signals, we present a simple and efficient strategy to derive human pituitary lineages from hPSCs using monolayer culture conditions suitable for cell manufacturing. We demonstrate that purified placode cells can be directed into pituitary fates using defined signals. hPSC-derived pituitary cells show basal and stimulus-induced hormone release in vitro and engraftment and hormone release in vivo after transplantation into a murine model of hypopituitarism. This work lays the foundation for future cell therapy applications in patients with hypopituitarism., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2016
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