embryonic pituitary gland

A micrograph of an embryonic pituitary gland that self-formed in an embryonic stem cell aggregate on day 13 of culture, oval-shaped pouches develop between the two layers of tissue. © Yoshiki Sasai (Nature 480, 57–62)

RIKEN’s recent success in growing a functional pituitary gland from stem cells could advance regenerative medicine and pave the way for new therapies to treat hormonal disorders.

Researchers at the RIKEN’s Center for Developmental Biology have developed a novel technique for growing stem cells in three-dimensional floating ‘clusters’. This has enabled them to create a version of the pituitary gland that is fully functional when transplanted into mice. The team had previously shown that stem cells grown in this way can organise themselves into functional eye and brain tissue. This new work represents a major breakthrough for stem cell science that could pave the way for future treatments.

The pituitary is a pea-sized gland which sits at the base of our brain and releases hormones including growth hormone, prolactin and follicle stimulating hormone (FSH) into our bloodstream.

These hormones play various roles in the body, ranging from the regulation of growth to the control of sex organ function, so any flaws in the system can have serious health consequences.

“Growth hormone deficiency could be a target of [stem] cell therapy,” said Yoshiki Sasai, one of the researchers involved.

The problem is getting the right cells to grow under laboratory conditions, as their development can be incredibly complicated.

The part of the pituitary containing the cells that make hormones develops when two layers of tissue (each made up of a different type of cells) come into contact and exchange chemical signals. This interaction leads to the formation of a small pouch that pinches off from the area in the growing embryo.

Sasai and his colleagues managed to replicate this process by stimulating clusters of stem cells with specific signalling molecules. They succeeded in generating both types of tissue which separated naturally into layers. Cells at the interface between the two layers then spontaneously formed oval-shaped pouches before differentiating into four distinct cell types, each of which began to synthesise and secrete a different hormone.

The cell clusters were then transplanted into the kidneys of mice whose pituitaries had been surgically removed. Normally these mice would die two months post-surgery, but the transplanted cells rescued the animals by restoring their hormone levels.

The breakthrough could open new avenues of treatment for hormonal disorders. It also represents a significant advance in using stem cells to generate complex three-dimensional structures, and is a step towards growing fully functional organs in the laboratory. “Regenerative medicine is proceeding in this direction,” says Sasai. “We are now developing computer-based models and simulations to facilitate the design of more complex organs.”

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