Sitting atop the kidneys, the adrenal gland plays a pivotal role in maintaining a healthy body. Responding to signals from the brain, the gland secretes hormones that support critical functions like blood pressure, metabolism, and fertility.
People with adrenal gland disorders, such as primary adrenal insufficiency, in which the gland does not release sufficient hormones, can suffer fatigue, dangerously low blood pressure, coma, and even death if untreated. No cure for primary adrenal insufficiency exists, and the lifelong hormone-replacement therapy used to treat it carries significant side effects.
A preferable alternative would be a regenerative medicine approach, regrowing a functional adrenal gland capable of synthesizing hormones and appropriately releasing them in tune with the brain’s feedback. With a new study in the journal Developmental Cell, researchers from the University of Pennsylvania School of Veterinary Medicine coaxed stem cells in a petri dish to divide, mature, and take on some of the functions of a human fetal adrenal gland, bringing that goal one step closer.
“This is a proof-of-principle that we can create a system grown in a dish that functions nearly identically to a human adrenal gland in the early stages of development,” says Kotaro Sasaki, senior author and an assistant professor at Penn Vet. “A platform like this could be used to better understand the genetics of adrenal insufficiency and even for drug screening to identify better therapies for people with these disorders.”
Sasaki says his team’s aim was to use human inducible pluripotent stem cells (iPSCs), which can give rise to a myriad of different cell types, to mimic the stages of normal human adrenal development. During this process, the cells would get directed to take on the characteristics of the adrenal gland.
To begin, the researchers used what’s known as an “organoid culture” system, in which cells grow first as a floating aggregate for three weeks, then on a membrane exposed to air on one side, promoting better survival and allowing them to proliferate in three dimensions. Utilizing a carefully selected growth medium, they prompted the iPSCs to elicit an intermediate tissue type in the adrenal development process, the posterior intermediate mesoderm (PIM).
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