Stem Cell Therapy Shows Promise as Treatment for Pituitary Gland Failure

By LabMedica International staff writers
Posted on 28 Jun 2016

The potential use of diverse hormone-releasing pituitary cells derived from human pluripotent stem cells (hPSCs) to treat hypopituitarism was demonstrated in a rat model.

Previous studies have derived pituitary cell lines from mouse and human stem cells using three-dimensional organoid cultures that mimicked the complex events underlying pituitary gland development in vivo. However, this inefficient and complicated approach relied on ill-defined cellular signals, lacked reproducibility, and was not scalable or suitable for clinical-grade cell manufacturing.

Image: An imunofluorescence image of hPSC-derived pituitary cells after 30 days of differentiation. The cells were stained for adrenocorticotropic hormone (red) and DNA/nucleus (blue). Cells similar to the ones shown in the picture were used for the transplantation studies (Photo courtesy of Dr. Bastian Zimmer, Sloan Kettering Institute for Cancer Research).

To correct these deficiencies, investigators at the Sloan Kettering Institute for Cancer Research (New York, NY, USA) developed a simple and efficient strategy to derive human pituitary lineages using monolayer culture conditions suitable for cell manufacturing.

The method, which was described in detail in the June 14, 2016, online edition of the journal Stem Cell Reports, was based on the precisely timed exposure of hPSCs to a few specific cellular signals that were known to play an important role during embryonic development. In particular, the relative composition of different hormonal cell types could be controlled by exposing hPSCs to different ratios of two proteins: FGF8 (fibroblast growth factor 8) and BMP2 (bone morphogenetic protein 2).

Pituitary cells derived from hPSCs showed basal and stimulus-induced hormone release in vitro and engraftment and hormone release in vivo after transplantation into a rat model of hypopituitarism. The grafted cells secreted adrenocorticotropic hormone, prolactin, and follicle-stimulating hormone, and they also triggered appropriate hormonal responses in the kidneys of the rats.

"The current treatment options for patients suffering from hypopituitarism, a dysfunction of the pituitary gland, are far from optimal," said first author Dr. Bastian Zimmer, a postdoctoral researcher at the Sloan Kettering Institute for Cancer Research. "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. Our findings represent a first step in treating hypopituitarism, but that does not mean the disease will be cured permanently within the near future. However, our work illustrates the promise of human pluripotent stem cells as it presents a direct path toward realizing the promise of regenerative medicine for certain hormonal disorders."

Related Links:
Sloan Kettering Institute for Cancer Research