05 February 2018

The first step to tissue-engineered adrenal glands

Researchers at Queen Mary University of London, working under the direction of Dr. Leonardo Guasti, used reprogrammed cells to create the first prototype of an artificial adrenal gland. These paired glands are located on the tops of both kidneys and synthesize steroid hormones that regulate the growth and development of the body, as well as its metabolism.

In their study, the authors described for the first time the production of steroid hormone-producing cells called "human induced steroidogenic cells" (hiSC) from cells isolated from the skin, blood and urine of healthy donors and patients with congenital diseases of the adrenal glands.

Reprogramming of cells was carried out by forcibly triggering the expression of one protein – steroidogenic factor-1 – and the activity of two signaling pathways mediated by protein kinase A and hormone releasing luteinizing hormone. The resulting cells expressed enzymes responsible for the production of steroid hormones and, which is a critical parameter, adequately responded to physiological stimuli, such as cortisol secretion in response to stimulation by adrenocorticotropic hormone.

Reprogrammed cells were also used to simulate diseases of the adrenal glands and as a platform for testing interventions developed in accordance with the principles of personalized therapy. The viability of the induced steroidogenic cells in vivo was tested by implantation in mice.

The steroid profile of induced steroidogenic cells obtained from the material of patients with monogenic adrenal gland disease (congenital adrenal hyperplasia) had changes characteristic of this disease. When an intact (mutation-free) gene was introduced into these cells, their steroid profile became normal, comparable to the profile of cells obtained from the material of healthy donors.

According to Dr. Guasti, the developed approach represents a fundamentally new concept of studying the adrenal glands, since the ability to receive donor-specific and functional cells will allow developing a new generation of methods for cell therapy of adrenal gland insufficiency and testing personalized interventions on cells reprogrammed from the patient's cells.

Article by Ruiz-Babot et al. Modeling Genital Adrenal Hyperplasia and Testing Interventions for Adrenal Insufficiency Using Donor-Specific Reprogrammed Cells is published in the journal Cell Reports.

Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of Queen Mary University of London: The first step in generating an artificial adrenal gland.


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