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Derivation of Diverse Hormone-Releasing Pituitary Cells from Human Pluripotent Stem Cells.
- Source :
-
Stem cell reports [Stem Cell Reports] 2016 Jun 14; Vol. 6 (6), pp. 858-872. - Publication Year :
- 2016
-
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.<br /> (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 2213-6711
- Volume :
- 6
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Stem cell reports
- Publication Type :
- Academic Journal
- Accession number :
- 27304916
- Full Text :
- https://doi.org/10.1016/j.stemcr.2016.05.005