SFEBES2016 Poster Presentations Adrenal and Steroids (41 abstracts)
Generation of human urine-derived steroidogenic cells through lineage conversion: A new technology to study the adrenal gland
Gerard Ruiz-Babot 1 , Irene Hadjidemetriou 1 , Sharon Jane Ajodha 1 , Lea Ghataore 2 , David Taylor 2 , Norman Taylor 2 , Mariya Balyura 3 , Stefan R Bornstein 3 & Leonardo Guasti 1
1Queen Mary University of London, London, UK; 2King’s College Hospital, London, UK; 3Technische Universität Dresden, London, Germany.
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. The adrenal cortex is the primary site of steroid synthesis. Adrenal insufficiency, which can be life threatening, is caused by a number of adrenal disorders, and lifelong management of these patients with exogenous steroids can be challenging. Our long-term goal is to develop novel personalized and curative treatments that use stem cells and cellular reprogramming to treat the many progressive and debilitating conditions affecting the adrenal cortex. Steroidogenic Factor-1 (SF1) is a transcription factor essential for both adrenal and gonadal development. SF1 positively regulates steroidogenic genes transcription and can be considered a true effector of cell fate as it starts a genetic program driving embryonic mesenchymal cells towards a steroidogenic phenotype/lineage. We have discovered that cells derived from urine (urine-derived stem cells, USCs) can be reprogrammed to a steroidogenic phenotype with a highly reproducible phenotype as assessed by changes in cell morphology, gene expression, activation of adrenal-specific signalling pathways and hormonal output. Urine is the perfect cell source reservoir as its harvest is the least invasive. In vivo transplantation experiments in nude mice using alginate-embedded reprogrammed human urine-derived steroidogenic cells are currently being performed to test the functionality of these cells in a more physiological environment. Moreover, USCs derived from patients with familial glucocorticoid deficiency (FGD) and congenital adrenal hyperplasia (CAH) are being isolated, amplified and banked and we are aiming to use the new genome editing tool CRISPR-Cas9 to repair the monogenic mutations occurring in these conditions. These will allow us to in vitro assess the hormonal profiles of affected versus CRISPR-Cas9 gene corrected cells, serving as a proof-of-concept of our technology.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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