A gland grows itself

Pituitary develops in a lab dish with chemical coaching

Researchers have grown a mouse pituitary gland for the first time from embryonic stem cells. Or rather, the pituitary gland grew itself, after Japanese researchers coaxed embryonic stem cells to form the type of tissues that normally surround the gland.

Japanese researchers grew this pituitary gland in the laboratory from embryonic stem cells. Here, hormone-producing cells called pituitary endocrine cells (tagged to glow red) are making a hormone called adrenocorticotropin. Yoshiki Sasai, RIKEN Center for Developmental Biology

The accomplishment, reported online November 9 in Nature, could be the first step toward replacement pituitary glands for people. Self-made glands growing in lab dishes may also help researchers learn how the organs develop inside the body.

“There’s a lot in it to be excited about, whether you’re a developmental biologist or interested in clinical applications,” says Sally Camper, a developmental geneticist at the University of Michigan in Ann Arbor. Camper has tried, and failed, to coax embryonic stem cells to form pituitary glands.

“It’s a gorgeous piece of work, and it’s just really, really exciting,” she says.

Scientists have persuaded stem cells to form particular types of tissues before, but growing a whole organ in a lab dish has been an elusive goal, says pediatric endocrinologist Mehul Dattani of the University College London Institute of Child Health and Great Ormond Street Hospital for Children in London.

What allowed Yoshiki Sasai of the RIKEN Center for Developmental Biology in Kobe, Japan, and colleagues to succeed where others have failed is that the group recreated conditions that exist in the part of the brain where the pituitary normally grows. The researchers used chemicals to coax mouse embryonic stem cells to form two types of brain tissue in a lab dish. Where those two tissues meet in the brain is where the pituitary forms, so the researchers manipulated conditions such that the tissues would form side-by-side. The researchers then gave the tissues a dose of Hedgehog, an important protein that directs development of many different tissues.

A fold of tissue called Rathke’s pouch spontaneously formed between the two tissues and eventually grew into a pituitary gland, complete with five different types of hormone-producing cells normally found in a naturally formed gland.

And, the dish-grown gland actually works. It secretes a hormone, called adrenocorticotropic hormone, both in a lab dish and when transplanted near the kidney in mice, which is more practical than trying to put the gland in its normal spot at the base of the brain.  

The pituitary also makes many other hormones that regulate growth, blood pressure, water retention, sex organ and thyroid function and pregnancy and milk production. Sasai says his group is testing to see if lab-grown glands can make all of the hormones.

Details of how the tissue’s interactions produce a pituitary gland are still a bit murky, says Dattani. “We’re beginning to get some idea, but we’re still a long way away. There’s still a lot of players left to be identified.”

Sasai hopes to produce human pituitary glands from human embryonic stem cells or from reprogrammed stem cells within the next three years.

Tina Hesman Saey is the senior staff writer and reports on molecular biology. She has a Ph.D. in molecular genetics from Washington University in St. Louis and a master’s degree in science journalism from Boston University.

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