Development of a transplantable bioartificial adrenal

Mariya Balyura, Dr. Vet. Med

Principal Investigator

  0351 458-6615 E-Mail

Evgeny Gelfgat, MD, PhD

  +49 (0) 351 796 5691 E-Mail

The proposed strategy for adrenal cell replacement therapy by transplanting a bioartificial adrenal system is built under the supervision of Dr. Barbara Ludwig – the head of islets transplantation unit, and Prof. Stefan R. Bornstein. This project is supported by the Deutsche Forschungsgemeinschaft (SFB-TRR 127 and KFO 252).

Adrenal insufficiency is a life-threatening disorder that requires a complex and permanent hormone replacement. All current replacement strategies suffer from numerous problems as they fail to restore circadian variations in hormone secretion. Therefore, adrenal cell transplantation could be a preferable therapeutic alternative for patients suffering from primary adrenal dysfunction. However, this strategy is critically limited by the lack of suitable donors of human organs and the requirement of chronic immunosuppression.

We have developed a three-dimensional sodium alginate encapsulated system, originally  designed for pancreatic islets, that provides sufficient immune-isolation while maintaining regular cell function. This concept has been tested successfully in various pre-clinical models of diabetes and in a first clinical case of type 1 diabetes. Based on this we aim to adopt this concept for the development of an adrenal cell replacement therapy for patients suffering from adrenal insufficiency. This may potentially allow for the restoration of HPA axis function and a possible curative strategy for these patients.

The present project utilizes latest technologies of cell encapsulation in order to renew the idea of adrenal cell replacement to generate a bioartificial adrenal transplant for safe and physiological hormone substitution. To this end, we isolated bovine adrenocortical cells, embedded them in alginate and achieved preserved functionality for 114 days.  Such a bioartificial adrenal was integrated in encapsulation device and transplanted into adrenalectomized rats. During the follow-up of > 20 days, the adrenal grafts maintained their morphology and function.