Scientists from Queen Mary University took a huge step toward creating an artificial adrenal gland by generating human induced steroidogenic cells (hiSCs) from fibroblasts, blood-, and urine-derived cells. Currently, adrenal insufficiency is managed by hormone replacement therapy. The ability to generate functional steroidogenic cells would help understand and develop therapeutics related to the complex feedback regulation of the hypothalamic-pituitary-adrenal axis, explains lead author Leonardo Guasti from Queen Mary's William Harvey Research Institute.
In the paper published in Cell Reports yesterday, the authors describe the generation of hiSCs from skin, blood, and urine of healthy donors and patients with congenital adrenal disorders. hiSCs were used to model adrenal diseases and used to assess personalized treatments. hiSCs were also shown to be viable when transplanted into the mouse kidney capsule and intra-adrenal.
Reprogramming was achieved by forcing the expression of a single protein (a transcription factor) and the activation of two signaling pathways. The newly generated hiSCs expressed the enzymes responsible for steroid production and crucially were responsive to physiological stimuli, such as the secretion of corticol upon ACTH stimulation.
The steroid profile of hiSCs generated from patients with congenital adrenal hyperplasia was altered, in keeping with their profile at diagnosis. When the non-mutated gene was re-introduced into these cells, the steroid profile was back to normal, and similar to that observed in hiSCs obtained from healthy donors.
"[This research] represents an entirely new concept for the study of the adrenal gland as the ability to generate donor-specific and functional adrenal-like cells will facilitate the next generation of cell-based treatments for adrenal insufficiency, the modeling of adrenal specific diseases, and the testing of personalized interventions on cells derived from patients," Guasti added.