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Modeling Congenital Adrenal Hyperplasia and Testing Interventions for Adrenal Insufficiency Using Donor-Specific Reprogrammed Cells
Adrenal insufficiency is managed by hormone replacement therapy, which is far from optimal; the ability to generate functional steroidogenic cells would offer a unique opportunity for a curative approach to restoring the complex feedback regulation of the hypothalamic-pituitary-adrenal axis. Here, w...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cell Press
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5809617/ https://www.ncbi.nlm.nih.gov/pubmed/29386111 http://dx.doi.org/10.1016/j.celrep.2018.01.003 |
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author | Ruiz-Babot, Gerard Balyura, Mariya Hadjidemetriou, Irene Ajodha, Sharon J. Taylor, David R. Ghataore, Lea Taylor, Norman F. Schubert, Undine Ziegler, Christian G. Storr, Helen L. Druce, Maralyn R. Gevers, Evelien F. Drake, William M. Srirangalingam, Umasuthan Conway, Gerard S. King, Peter J. Metherell, Louise A. Bornstein, Stefan R. Guasti, Leonardo |
author_facet | Ruiz-Babot, Gerard Balyura, Mariya Hadjidemetriou, Irene Ajodha, Sharon J. Taylor, David R. Ghataore, Lea Taylor, Norman F. Schubert, Undine Ziegler, Christian G. Storr, Helen L. Druce, Maralyn R. Gevers, Evelien F. Drake, William M. Srirangalingam, Umasuthan Conway, Gerard S. King, Peter J. Metherell, Louise A. Bornstein, Stefan R. Guasti, Leonardo |
author_sort | Ruiz-Babot, Gerard |
collection | PubMed |
description | Adrenal insufficiency is managed by hormone replacement therapy, which is far from optimal; the ability to generate functional steroidogenic cells would offer a unique opportunity for a curative approach to restoring the complex feedback regulation of the hypothalamic-pituitary-adrenal axis. Here, we generated human induced steroidogenic cells (hiSCs) from fibroblasts, blood-, and urine-derived cells through forced expression of steroidogenic factor-1 and activation of the PKA and LHRH pathways. hiSCs had ultrastructural features resembling steroid-secreting cells, expressed steroidogenic enzymes, and secreted steroid hormones in response to stimuli. hiSCs were viable when transplanted into the mouse kidney capsule and intra-adrenal. Importantly, the hypocortisolism of hiSCs derived from patients with adrenal insufficiency due to congenital adrenal hyperplasia was rescued by expressing the wild-type version of the defective disease-causing enzymes. Our study provides an effective tool with many potential applications for studying adrenal pathobiology in a personalized manner and opens venues for the development of precision therapies. |
format | Online Article Text |
id | pubmed-5809617 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Cell Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-58096172018-02-14 Modeling Congenital Adrenal Hyperplasia and Testing Interventions for Adrenal Insufficiency Using Donor-Specific Reprogrammed Cells Ruiz-Babot, Gerard Balyura, Mariya Hadjidemetriou, Irene Ajodha, Sharon J. Taylor, David R. Ghataore, Lea Taylor, Norman F. Schubert, Undine Ziegler, Christian G. Storr, Helen L. Druce, Maralyn R. Gevers, Evelien F. Drake, William M. Srirangalingam, Umasuthan Conway, Gerard S. King, Peter J. Metherell, Louise A. Bornstein, Stefan R. Guasti, Leonardo Cell Rep Article Adrenal insufficiency is managed by hormone replacement therapy, which is far from optimal; the ability to generate functional steroidogenic cells would offer a unique opportunity for a curative approach to restoring the complex feedback regulation of the hypothalamic-pituitary-adrenal axis. Here, we generated human induced steroidogenic cells (hiSCs) from fibroblasts, blood-, and urine-derived cells through forced expression of steroidogenic factor-1 and activation of the PKA and LHRH pathways. hiSCs had ultrastructural features resembling steroid-secreting cells, expressed steroidogenic enzymes, and secreted steroid hormones in response to stimuli. hiSCs were viable when transplanted into the mouse kidney capsule and intra-adrenal. Importantly, the hypocortisolism of hiSCs derived from patients with adrenal insufficiency due to congenital adrenal hyperplasia was rescued by expressing the wild-type version of the defective disease-causing enzymes. Our study provides an effective tool with many potential applications for studying adrenal pathobiology in a personalized manner and opens venues for the development of precision therapies. Cell Press 2018-01-30 /pmc/articles/PMC5809617/ /pubmed/29386111 http://dx.doi.org/10.1016/j.celrep.2018.01.003 Text en © 2018 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Ruiz-Babot, Gerard Balyura, Mariya Hadjidemetriou, Irene Ajodha, Sharon J. Taylor, David R. Ghataore, Lea Taylor, Norman F. Schubert, Undine Ziegler, Christian G. Storr, Helen L. Druce, Maralyn R. Gevers, Evelien F. Drake, William M. Srirangalingam, Umasuthan Conway, Gerard S. King, Peter J. Metherell, Louise A. Bornstein, Stefan R. Guasti, Leonardo Modeling Congenital Adrenal Hyperplasia and Testing Interventions for Adrenal Insufficiency Using Donor-Specific Reprogrammed Cells |
title | Modeling Congenital Adrenal Hyperplasia and Testing Interventions for Adrenal Insufficiency Using Donor-Specific Reprogrammed Cells |
title_full | Modeling Congenital Adrenal Hyperplasia and Testing Interventions for Adrenal Insufficiency Using Donor-Specific Reprogrammed Cells |
title_fullStr | Modeling Congenital Adrenal Hyperplasia and Testing Interventions for Adrenal Insufficiency Using Donor-Specific Reprogrammed Cells |
title_full_unstemmed | Modeling Congenital Adrenal Hyperplasia and Testing Interventions for Adrenal Insufficiency Using Donor-Specific Reprogrammed Cells |
title_short | Modeling Congenital Adrenal Hyperplasia and Testing Interventions for Adrenal Insufficiency Using Donor-Specific Reprogrammed Cells |
title_sort | modeling congenital adrenal hyperplasia and testing interventions for adrenal insufficiency using donor-specific reprogrammed cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5809617/ https://www.ncbi.nlm.nih.gov/pubmed/29386111 http://dx.doi.org/10.1016/j.celrep.2018.01.003 |
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