Stem cells restored the pituitary gland
Scientists at the Sloan Kettering Institute of Cancer Research, working under the guidance of Professor Lorenz Studer, have created functional pituitary tissue from human stem cells. When transplanted to rats with simulated hypopituitarism (pituitary insufficiency) – a disease associated with stunting and premature aging – the tissue grown in the laboratory provided normal hormone release.
An immunofluorescence microscope image of pituitary cells obtained from human pluripotent stem cells 30 days after differentiation. The cells are colored by adrenocorticotropic hormone (red) and nuclear DNA (blue). Similar cells were used for transplantation to rats.
The pituitary gland is a gland localized in the brain and is the main regulator of hormone production in the body, releasing hormones that play key roles in many vital processes. The causes of hypopituitarism may be tumors, genetic defects, brain injuries, immune and infectious diseases, as well as radiotherapy. The consequences of pituitary dysfunction can vary widely and take particularly severe forms in children who may suffer from severe impairments of learning ability, growth, skeletal formation, as well as puberty and sexual function.
Currently, patients with hypopituitarism are forced to receive expensive hormone replacement therapy throughout their lives, poorly reproducing complex patterns of hormone secretion in the body, fluctuating depending on circadian rhythms and responding to feedback from other organs. On the contrary, cell replacement therapy is potentially capable of permanently restoring the natural patterns of hormone secretion, eliminating the need for expensive lifelong therapy.
Recently, researchers have developed a procedure for obtaining pituitary cells from human pluripotent stem cells by creating organoid cultures that reproduce the three-dimensional organization of the developing pituitary gland. However, this inefficient and complex approach is based on poorly described cellular signals, has low reproducibility, cannot be scaled and is not suitable for the production of cells suitable for clinical use.
The simple, effective and reliable strategy proposed by the authors makes it possible to overcome all these limitations. Instead of reproducing the complex three-dimensional structure of the developing pituitary gland, the new approach is based on precisely timed exposure of human pluripotent cells to several specific cellular signals that play important roles in embryonic development.
The effect of these proteins triggers the differentiation of stem cells into different types of pituitary cells that release hormones necessary for the growth and development of tissues (growth hormone), the development of stress reactions (adrenocorticotropic hormone) and reproductive function (prolactin, follicle-stimulating hormone, luteinizing hormone). Moreover, the cells obtained using this method released different amounts of hormones in response to known chemical feedback signals generated by other organs.
To test the therapeutic potential of the new approach, the authors transplanted pituitary cells grown from stem cells under the skin of rats with previously surgically removed pituitary glands. As a result, cell transplants not only secreted adrenocorticotropic hormone, prolactin and follicle-stimulating hormone, but also triggered adequate hormonal reactions from the kidneys.
The researchers also managed to control the quantitative ratio of different types of hormone-producing cells by influencing pluripotent stem cells with different ratios of two proteins: fibroblast growth factor-8 and bone morphogenetic protein-2. This indicates the possibility of creating individual transplants for patients with different types of hypopituitarism.
In the future, the authors plan to improve the protocol in order to obtain pure populations of various hormone-producing cells, which will allow for the formation of personalized transplants with high accuracy. They also plan to test the approach on more clinically adequate animal models with pituitary injuries caused by radiotherapy and to inject grafts not under the skin, but directly into the pituitary gland or surrounding tissue. These studies may be important for people who have had cancer, since hypopituitarism is one of the main causes of a decrease in the quality of life after radiotherapy of the brain.
Article by Bastian Zimmer et al. Derivation of Diverse Hormone-Releasing Pituitary Cells from Human Pluripotent Stem Cells is published in the journal Stem Cell Reports.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on EurekAlert!: Pituitary tissue grown from human stem cells releases hormones in rats.
15.06.2016