دورية أكاديمية
Generation of glucocorticoid-producing cells derived from human pluripotent stem cells
| العنوان: | Generation of glucocorticoid-producing cells derived from human pluripotent stem cells |
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| المؤلفون: | Gerard Ruiz-Babot, Ariane Eceiza, Fernando Abollo-Jiménez, Maria Malyukov, Diana L. Carlone, Kleiton Borges, Alexandra Rodrigues Da Costa, Shamma Qarin, Takuya Matsumoto, Ryuji Morizane, William C. Skarnes, Barbara Ludwig, Paul J. Chapple, Leonardo Guasti, Helen L. Storr, Stefan R. Bornstein, David T. Breault |
| المصدر: | Cell Reports: Methods, Vol 3, Iss 11, Pp 100627- (2023) |
| بيانات النشر: | Elsevier, 2023. |
| سنة النشر: | 2023 |
| المجموعة: | LCC:Biotechnology LCC:Biochemistry LCC:Science |
| مصطلحات موضوعية: | CP: Stem cell, Biotechnology, TP248.13-248.65, Biochemistry, QD415-436, Science |
| الوصف: | Summary: Adrenal insufficiency is a life-threatening condition resulting from the inability to produce adrenal hormones in a dose- and time-dependent manner. Establishing a cell-based therapy would provide a physiologically responsive approach for the treatment of this condition. We report the generation of large numbers of human-induced steroidogenic cells (hiSCs) from human pluripotent stem cells (hPSCs). Directed differentiation of hPSCs into hiSCs recapitulates the initial stages of human adrenal development. Following expression of steroidogenic factor 1, activation of protein kinase A signaling drives a steroidogenic gene expression profile most comparable to human fetal adrenal cells, and leads to dynamic secretion of steroid hormones, in vitro. Moreover, expression of the adrenocorticotrophic hormone (ACTH) receptor/co-receptor (MC2R/MRAP) results in dose-dependent ACTH responsiveness. This protocol recapitulates adrenal insufficiency resulting from loss-of-function mutations in AAAS, which cause the enigmatic triple A syndrome. Our differentiation protocol generates sufficient numbers of hiSCs for cell-based therapy and offers a platform to study disorders causing adrenal insufficiency. Motivation: Adrenal insufficiency is a life-threatening condition resulting from the inability to produce steroid hormones in a dose and time-dependent manner. The ability to generate cells that produce cortisol in response to adrenocorticotrophic hormone (ACTH), the main regulator of glucocorticoid production in humans, combined with the development of encapsulation and immunoprotecting technologies, will open future opportunities to treat this condition using cell-based therapies. Current protocols have demonstrated the generation of fetal-like steroid-producing cells from hPSCs. However, the resulting cells fail to secrete cortisol, the main glucocorticoid in humans. We therefore sought to develop a protocol that enables the generation of billions of cells that produce cortisol and can respond to ACTH stimulation. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2667-2375 |
| Relation: | http://www.sciencedirect.com/science/article/pii/S2667237523002916; https://doaj.org/toc/2667-2375 |
| DOI: | 10.1016/j.crmeth.2023.100627 |
| URL الوصول: | https://doaj.org/article/6ac601e73ba74f568125dbf81561e3a8 |
| رقم الأكسشن: | edsdoj.6ac601e73ba74f568125dbf81561e3a8 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 26672375 |
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| DOI: | 10.1016/j.crmeth.2023.100627 |