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‘Pituitary gland in a dish’ makes up for lost hormones

php8xDYjIAM.jpgA pituitary gland made from stem cells may some day treat diseases in which people produce little or none of the sex, growth or stress hormones that the organ normally churns out.

Japanese scientists have coaxed mouse embryonic stem cells into forming a working anterior pituitary gland, made of several different kinds of hormone-producing cells. When transplanted into mice, the engineered organ produces a stress hormone called corticotrophin.

The results, from Yoshiki Sasai’s team at RIKEN Center for Developmental Biology in Kobe, Japan, are published online today in Nature. The same team created a retina from mouse stem cells, then the most complex tissue yet made from stem cells.

Sasai’s team engineered both tissues in three-dimensional cell culture structures that provide support and needed growth factors. To develop properly, the pituitary gland was grown nestled up to stem cells that developed into neurons. This contact mimics the situation in normal pituitary development in which the anterior pituitary gland (which releases growth, sex and stress hormones) develops from the same tissue that makes the oral cavity, while the posterior pituitary (which is involved in regulating fluid balance) forms from neural tissue.

To simulate this in the laboratory, Sasai’s team transformed mouse stem cells into both kinds of tissues, side by side. After three weeks, the cells at the intersection had formed an anterior pituitary gland made up of several kinds of hormone-releasing cells. When stimulated with another hormone, the engineered cells produced the stress hormone corticotrophin. Transplanted beside the kidneys of mice lacking pituitary glands (transplanting it where the pituitary normally resides would have destroyed too many blood vessels), the engineered organs produced the same hormone. These mice also were more active and lived longer than mice that didn’t receive a transplant.

Mehul Dattani, a Professor of Paediatric Endocrinology at University College London, says pituitary glands made from human stem cells could form a treatment for hypopituitarism, a suite of endocrine disorders caused by low levels of sex, growth and stress hormones. Current treatments involve a lifelong course of potent replacement hormones, and an engineered pituitary gland could rid patients of this burden.

Before this happens, scientists will need to figure out how to transform human embryonic stem cells (and perhaps reprogrammed pluripotent stem cells made from adult tissue) into pituitary glands. Given the fast pace of stem-cell research, I would not be surprised if Sasai’s team and others were already working on forging pituitary glands from human stem cells.

A bigger hurdle to engineering human pituitary glands (besides the safety caveats that come with stem-cell treatments) could be wiring them up properly, Dattani says. The hypothalamus controls the release of many pituitary hormones, and it could prove difficult getting lab-made pituitary glands to talk to the hypothalamus, he says.

Image of pituitary cells (red) producing adrenocorticotropin courtesy Yoshiki Sasai, RIKEN Center for Developmental Biology


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