Bovine cells show promise as treatment for adrenal insufficiency

Last Updated: 2015-02-25

By Will Boggs MD

NEW YORK (Reuters Health) - Bovine adrenocortical cells encapsulated in alginate survive and function when transplanted into a rat model of adrenal insufficiency, researchers report.

"For the bioartificial adrenal, the next step will be larger animal models before moving into humans," Dr. Stefan R. Bornstein, from Technische Universitaet Dresden in Germany, told Reuters Health by email. "Endocrine cell replacement will become possible without any immunosuppression."

Adrenal gland transplantation for patients with adrenal insufficiency is extremely limited by the lack of human donor organs, the surgical difficulties attending adrenal transplantation, and the requirement for chronic immunosuppression.

As part of their effort to create a long-lasting, immune-isolated, and functional bioartificial adrenal, Dr. Bornstein and colleagues encapsulated bovine adrenocortical cells in alginate, a clinically approved immuno-isolating biopolymer, and tested their functionality and efficacy after implantation into bilaterally adrenalectomized rats.

They were able to create functional 3-dimensional cultures of adrenal cells any time within the first seven days after their isolation, according to the online February 9 PNAS Early Edition report.

In vitro, these bioartificial adrenals showed stable cortisol production that continued for at least 70 days (the end of their observation period) while maintaining their ability to respond to adrenocorticotropic hormone (ACTH) stimulation.

The adrenal cells continued to function after implantation into adrenalectomized rats, unlike free cells that showed a downward trend of cortisol levels.

All animals receiving the encapsulated bovine cell implants survived until the end of the observation period with sustained cortisol levels and consistent responsiveness to ACTH stimulation.

Results were similar when researchers implanted the encapsulated cells in a special oxygenated immune-isolating device.

"In conclusion," the authors note, "transplantation of a bioartificial adrenal with xenogeneic cells may be a treatment option for patients with adrenocortical insufficiency and other stress-related disorders. Furthermore, this model provides a microenvironment that ensures 3D cell-cell interactions as a unique tool to investigate new insights into cell biology, differentiation, tissue organization, and homeostasis."

"Although encapsulated bovine cells may be used in humans, it would be better to use human adrenocortical cells, which can be derived from stem cells," Dr. James C. Dunn, from the University of California, Los Angeles, who previously showed that adrenocortical cell transplantation could reverse adrenal failure in a mouse model, told Reuters Health by email. "The encapsulation technology also needs to be improved - previous experience with pancreatic islets encapsulation shows that alginate is not a long-term solution for treatment of diabetes."

"Adrenocortical cell therapy is feasible in animal models, but more work is needed before human therapy becomes a clinical reality," Dr. Dunn concluded. "This could certainly replace the need for lifetime medications."

The International Fund for Congenital Adrenal Hyperplasia and European Society for Pediatric Endocrinology supported this research. The authors report no disclosures.

SOURCE: http://bit.ly/1wpnF0z

PNAS 2015.