Lab-grown adrenal glands could help treat hormone-related conditions

Functional adrenal glands have been grown in the lab by coaxing a type of stem cell to develop in a certain way by constantly tweaking the mix of chemicals they are bathed in

Tiny human adrenal glands similar to those found in 4-month-old fetuses have been grown from stem cells in the lab for the first time. The achievement may help to develop treatments for conditions in which these glands don’t function properly.

Adrenal glands are located in the kidneys and make molecules that are involved in our metabolism, our response to stress and the production of sex hormones.

Previous attempts to grow small versions of the glands from induced pluripotent stem (IPS) cells – adult cells that have been coaxed to revert to a form where they have the potential to develop into almost any cell type – have failed to demonstrate that what was grown was similar to those found in the body.

Now, Kotaro Sasaki at the University of Pennsylvania and his colleagues have grown IPS cells derived from the blood of three people into adrenal glands that are roughly 2 millimetres wide.

The lab-grown glands contained all the major cell types and features found in the glands of a fetus in the second trimester of pregnancy. The pattern of gene activity was also similar between lab-grown glands and the fetal ones. What’s more, the lab-grown glands produced the stress-linked hormone cortisol, as well as pregnenolone, a molecule that the body uses to make many hormones, including testosterone, oestrogen and progesterone.

“Our adrenal glands have pretty much everything you’d see in that of a fetus during early development,” says Sasaki. “As adrenal glands produce many critical hormones that are essential for life, having an accurate model of how they develop will provide a way to understand how we can treat conditions where people lack important adrenal hormones like cortisol.”

It could also open the door to therapy where you grow a person’s own cells into adrenal tissue that you implant back into the body, he says, which could help with hormone-related conditions like polycystic ovary syndrome or high blood pressure.

The team spent three years establishing the precise cocktail of growth factor substances and chemicals that needed to be added to enable single IPS cells to each grow into fetal adrenal glands over six weeks.

“Roughly every three days, we have to exchange the mixture and tweak the ratio of around five chemicals that are in the lab dish,” says Sasaki.

“This study is impactful as it is the first one to generate fetal adrenal cells from inducible pluripotent stem cells,” says Leonardo Guasti at Queen Mary University of London.

However, the adrenal glands would need to reach the postnatal stage rather than the fetal stage for us to be able to use the technique to develop cell-based treatments for conditions that involve the adrenal glands, he says.

Sasaki and his colleagues are working on extending that development time.

Journal reference: bioRxiv , DOI: 10.1101/2022.10.31.514433

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