SFEBES2017 Applied Physiology Workshop Tissue Engineering for Regenerative Medicine in Endocrinology (3 abstracts)
Queen Mary University of London, London, UK.
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 restoring the complex feedback regulation of the hypothalamicpituitaryadrenal 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 PKA and LHRH pathways. hiSCs had ultrastructural features resembling steroid-secreting cells, expressed steroidogenic enzymes and secreted steroid hormones in response to stimuli. hiSCs successfully engrafted into the mouse kidney capsule and underwent intra-adrenal differentiation. 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 to study adrenal pathobiology in a personalized manner and opens venues for the development of precision therapies.