MON-500 Adrenal Bioprinted Tissue Therapeutics Restore Function in Murine Models of Primary Adrenal Insufficiency

Abstract Disclosure: H. Soliman: None. Z.A. Bazzi: None. O. Nemirovsky: None. S. Keshvani: None. C. Song: None. N.A. Chan: None. S. Gicole: None. R.B. Jalili: None. S. Wadsworth: None. C.T. Dickman: None. Primary adrenal insufficiency, caused by either autoimmune Addison’s disease or congenital adrenal hyperplasia, is a life-threatening condition that requires lifelong adrenal hormone replacement. Current hormone replacement therapies have a high treatment burden and fail to mimic the natural circadian rhythms of hormone secretion. Transplanting functional adrenal cells has the potential to restore the natural hypothalamic-pituitary-adrenal (HPA) axis feedback loop, enabling dynamic hormonal regulation that mimics physiological function rather than relying on fixed-dose steroid replacement. An allogeneic cell therapy that achieves this without the need for chronic immune suppression could be a breakthrough in the treatment of primary adrenal insufficiency. Adrenal Bioprinted Tissue Therapeutics (BTTs) were developed using primary human adrenocortical cells with Aspect Biosystems’ full-stack tissue therapeutic platform, which incorporates proprietary bioprinting technology. These cells were encapsulated in a cell-supporting biomaterial with an immunoprotective outer shell. In vitro assessment of these BTTs indicated that the encapsulated adrenal cells were viable for extended durations and able to sense exogenously administered adrenocorticotrophic hormone (ACTH) and respond by releasing cortisol. Implantation of these xenogeneic adrenal BTTs in adrenalectomized mice led to a dose-dependent, rapid, marked, and sustained responsive elevation of plasma cortisol and reduction in plasma ACTH, as well as an increase in survival. There was a robust response to exogenously administered ACTH resulting in a significant increase in plasma cortisol in mice implanted with adrenal BTTs. ACTH responsive cortisol secretion was observed through study end at six months. To assess whether implanted adrenal BTTs respond to physiological circadian fluctuations in endogenous mouse ACTH levels, plasma cortisol and ACTH were measured mornings and evenings and showed that plasma cortisol levels followed the same secretion pattern as endogenous ACTH in the adrenalectomized mice, indicating responsiveness of the implanted BTTs to physiological fluctuations in ACTH. Adrenal BTTs retrieved from mice at termination after six months demonstrated high viability and remained responsive to in vitro incubation with ACTH. These results indicate that Aspect Biosystems’ adrenal BTTs can restore precise ACTH responsive adrenal function with appropriate circadian rhythm in in vivo models of primary adrenal insufficiency. Such an approach could revolutionize therapy for patients with primary adrenal insufficiency. Presentation: Monday, July 14, 2025