Generation of Induced Steroidogenic Cells from Humans: Modelling Genetic Adrenal Disorders

Presentation Number: MON 397
Date of Presentation: April 3rd, 2017

Gerard Ruiz-Babot*1, Mariya Balyura2, Irene Hadjidemetriou1, Lea Ghataore3, David Taylor3, Sharon Jane Ajodha4, Norman Taylor3, Louise A Metherell5, Umasuthan Srirangalingam6, Gerard S Conway7, Stefan Richard Bornstein8 and Leonardo Guasti5
1William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, 2University Hospital Carl Gustav Carus, Department of Medicine III, Technische Universität Dresden, Dresden (Germany), 3Department of Clinical Biochemistry, King's College Hospital, London (UK), 4William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UNITED KINGDOM, 5William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom, 6Department of Endocrinology, University College London Hospitals, London UK, Kent, UNITED KINGDOM, 7Department of Endocrinology, University College London Hospitals, London UK, London, United Kingdom, 8University Hospital Carl Gustav Carus, Department of Medicine III, Technische Universität Dresden, Dresden (Germany), Dresden, Germany

Abstract

Cellular reprogramming describes the process where a fully differentiated, specialized cell type is induced to transform into a different cell. Cell reprogramming techniques can become powerful tools for modelling diseases, drug testing and for personalized cellular therapy.

Our aim was to develop a robust reprogramming protocol to generate functional steroidogenic cells from a variety of human cell sources (skin, blood and urine): through a trial-and-error approach we have devised a strategy whereby forced expression of Steroidogenic Factor-1 (SF1) together with the activation of cAMP-PKA pathway and in the presence of LHRH induced a steroidogenic-like phenotype as assessed by changes in cell morphology, gene expression, activation and responsiveness of adrenal-specific signalling pathways and hormonal output.

As urine is the perfect cell source reservoir as its harvest is the least invasive, urine-derived stem cells (USCs) were established from patients with familial glucocorticoid deficiency (FGD) and congenital adrenal hyperplasia (CAH) with different genetic defects.

This is the first study showing feasibility of adrenal diseases modelling using patients’ derived cells.

 

Nothing to Disclose: GR, MB, IH, LG, DT, SJA, NT, LAM, US, GSC, SRB, LG