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Ruiz-Babot, G.* ; Balyura, M.* ; Hadjidemetriou, I.* ; Ajodha, S.J.* ; Taylor, D.R.* ; Ghataore, L.* ; Taylor, N.F.* ; Schubert, U.* ; Ziegler, C.G.* ; Storr, H.L.* ; Druce, M.R.* ; Gevers, E.F.* ; Drake, W.M.* ; Srirangalingam, U.* ; Conway, G.S.* ; King, P.J.* ; Metherell, L.A.* ; Bornstein, S.R. ; Guasti, L.*

Modeling congenital adrenal hyperplasia and testing interventions for adrenal insufficiency using donor-specific reprogrammed cells.

Cell Rep. 22, 1236-1249 (2018)
Publ. Version/Full Text Research data DOI
Open Access Gold
Creative Commons Lizenzvertrag
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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Nr5a1 ; Adrenal Cortex ; Adrenal Insufficiency ; Congenital Adrenal Hyperplasia ; Disease Modeling ; Reprogramming ; Steroidogenic Cells ; Steroidogenic Factor 1 ; Transplantation ; Urine-derived Stem Cells; Pluripotent Stem-cells; Steroidogenic Cells; Adrenocortical-cells; Endothelial-cells; Mesenchymal Cells; Differentiation; Alginate; Factor-1; Lineage; Cortex
ISSN (print) / ISBN 2211-1247
e-ISSN 2211-1247
Journal Cell Reports
Quellenangaben Volume: 22, Issue: 5, Pages: 1236-1249 Article Number: , Supplement: ,
Publisher Cell Press
Publishing Place Cambridge
Reviewing status Peer reviewed
Institute(s) Institute for Pancreatic Beta Cell Research (IPI)