Yale investigators have developed a multistep process that models the biological instructions to create parathyroid gland cells from pluripotent stem cells, a significant milestone along the path toward helping people who lack the hormones released by parathyroid glands.
In a study published Aug. 18 in the journal Endocrinology with funding from Women’s Health Research at Yale, the authors demonstrated a highly reproducible technique for creating a cell that can produce RNA capable of manufacturing parathyroid hormone for people — mostly women — who suffer from missing or malfunctioning parathyroid glands. RNA serves as a messenger carrying instructions from DNA to produce proteins including hormones, substances secreted into the blood to regulate bodily functions.
This marks the latest development in senior author Dr. Diane Krause’s efforts to achieve a cure for a condition known as hypoparathyroidism, in which patients lack parathyroid hormone (PTH), leading to calcium deficiency and many health problems, from painful muscle spasms to heart failure.
“A major obstacle for this type of research is demonstrating the ability to reproduce the technique in other laboratories,” said Dr. Krause, Professor of Laboratory Medicine, Cell Biology, and Pathology and Associate Director of the Yale Stem Cell Center. “We were able to show our protocol’s success with two different cell types in our lab as well as in the laboratory of our partners at Children’s Hospital of Philadelphia.” Colleagues from the University of California, San Francisco provided additional critical assistance.
Women in the United States suffer from thyroid disease at rates up to eight times higher than men. Women develop thyroid cancer at a rate three times higher than men, often requiring the surgical removal of the thyroid gland as well as the smaller, often embedded parathyroid glands responsible for maintaining the body’s calcium levels.
Building on research developed in part by three Women’s Health Research at Yale grants, Dr. Krause’s team manipulated what are known as pluripotent stem cells through stages of development so that they could eventually produce parathyroid hormone. Pluripotent stem cells are the body’s basic, convertible building blocks that have the potential for becoming any of the body’s specialized cells, such as those that form bone, heart tissue, or, in this case, parathyroid-like cells.
“Our success would not have been possible without generous support from Women’s Health Research at Yale,” Krause said.
Dr. Krause has recently received a two-year grant from the National Cancer Institute to continue this work, including the first-ever single-cell analysis of normal human parathyroid tissue to better guide efforts toward developing parathyroid-like cells that produce functional levels of PTH when injected into the body.
“These exciting results are the product of years of careful effort by Dr. Krause and her colleagues in guiding the slow and steady progress of science,” said WHRY Director Carolyn M. Mazure, Ph.D. “This is just the latest example of how early investment and dedication continues advancement toward life-changing results.”
Other authors on the study include Betty R. Lawton and Courtney E. Gibson of Yale, Corine Martineau and Michael A. Levine of the Children’s Hospital of Philadelphia, and Julie Ann Sosa and Sanziana Roman of the University of California, San Francisco.