Project A05

Cell-based, immune-protective therapy for adrenal insufficiency

Project A05 aims to develop a physiological and long-term therapy option for patients with primary adrenal insufficiency. The current standard therapy with exogenous steroid hormones cannot completely replace central aspects of natural hormone regulation, such as the circadian rhythm and stress-dependent adaptation. The project therefore pursues a cell-based approach to restore endogenous hormone production.

During the first two funding periods, a robust protocol for the production of functional porcine adrenal cell spheroids was established. These spheroids exhibit zone-specific steroidogenesis, respond to physiological stimuli and were able to functionally compensate for the consequences of adrenal insufficiency in preclinical animal models. Their functionality was maintained over the long term by encapsulation in alginate.

In the final funding period, the focus is on the translational further development of this approach. The adrenal spheroids are combined with a macro-encapsulating immune barrier in the form of a macro chamber and tested for function, safety and biocompatibility in preclinical small and large animal models.

Objectives

(I) Functional adrenal cell spheroids. Establishment of stable, hormone-producing adrenal cell clusters as the basis for cell-based replacement therapy.

(II) Immunoprotective macro chamber. Combination of adrenal cell spheroids with a scalable, macro-encapsulating macro chamber and preclinical analysis of function and biocompatibility.

(III) Preclinical validation. Investigation of the efficacy, safety and long-term stability of the cell-based macro chamber in a porcine model of adrenal insufficiency.

© SFB/TRR 205