Generating New Pituitary Tissue in Mice

Researchers have announced another step forward in the development of methods of regeneration that should one day encompass all tissue types and organs in the body. This time the pituitary gland is the target, and the approach used here well illustrates the point that engineered replacements do not have to be in any way similar to the organ they are replacing. They just have to carry out the same functions.

Researchers have successfully used human stem cells to generate functional pituitary tissue that secretes hormones important for the body's stress response as well as for its growth and reproductive functions. When transplanted into rats with hypopituitarism the lab-grown pituitary cells promoted normal hormone release. "The current treatment options for patients suffering from hypopituitarism, a dysfunction of the pituitary gland, are far from optimal. Cell replacement could offer a more permanent therapeutic option with pluripotent stem cell-derived hormone-producing cells that functionally integrate and respond to positive and negative feedback from the body. Achieving such a long-term goal may lead to a potential cure, not only a treatment, for those patients."

The pituitary gland is the master regulator of hormone production in the body, releasing hormones that play a key role in bone and tissue growth, metabolism, reproductive functions, and the stress response. Hypopituitarism can be caused by tumors, genetic defects, brain trauma, immune and infectious diseases, or radiation therapy. The consequences of pituitary dysfunction are wide ranging. Currently, patients with hypopituitarism must take expensive, lifelong hormone replacement therapies that poorly mimic the body's complex patterns of hormone secretion that fluctuates with circadian rhythms and responds to feedback from other organs. By contrast, cell replacement therapies hold promise for permanently restoring natural patterns of hormone secretion while avoiding the need for costly, lifelong treatments.

Recently, scientists developed a procedure for generating pituitary cells from human pluripotent stem cells - an unlimited cell source for regenerative medicine - using organoid cultures that mimic the 3D organization of the developing pituitary gland. However, this approach is inefficient and complicated. To address these limitations, researchers developed a simple, efficient, and robust stem cell-based strategy for reliably producing a large number of diverse, functional pituitary cell types suitable for therapeutic use. Instead of mimicking the complex 3D organization of the developing pituitary gland, this approach relies on the precisely timed exposure of human pluripotent stem cells to a few specific cellular signals that are known to play an important role during embryonic development. Exposure to these proteins triggered the stem cells to turn into different types of functional pituitary cells.

To test the therapeutic potential of this approach, the researchers transplanted the stem cell-derived pituitary cells under the skin of rats whose pituitary gland had been surgical removed. The cell grafts not only secreted adrenocorticotropic hormone, prolactin, and follicle-stimulating hormone, but they also triggered appropriate hormonal responses in the kidneys. The researchers were also able to control the relative composition of different hormonal cell types simply by exposing human pluripotent stem cells to different ratios of two proteins: fibroblast growth factor 8 and bone morphogenetic protein 2. This finding suggests their approach could be tailored to generate specific cell types for patients with different types of hypopituitarism.

Link: http://www.eurekalert.org/pub_releases/2016-06/cp-ptg060716.php

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