Primary adrenal insufficiency is a life-threatening disorder, which requires lifelong
hormone replacement therapy.
Transplantation of xenogeneic adrenal cells is a potential alternative approach for the treatment of
adrenal insufficiency. For a successful outcome of this replacement
therapy, transplanted cells should provide adequate
hormone secretion and respond to adrenal physiological stimuli. Here, we describe the generation and characterization of primary porcine adrenal spheroids capable of replacing the function of adrenal glands in vivo. Cells within the spheroids morphologically resembled adult adrenocortical cells and synthesized and secreted adrenal
steroid hormones in a regulated manner. Moreover, the embedding of the spheroids in
alginate led to the formation of cellular elongations of steroidogenic cells migrating centripetally towards the inner part of the slab, similar to zona Fasciculata cells in the intact organ. Finally,
transplantation of adrenal spheroids in adrenalectomized SCID mice reversed the
adrenal insufficiency phenotype, which significantly improved animals' survival. Overall, such adrenal models could be employed for disease modeling and
drug testing, and represent the first step toward potential clinical trials in the future.