Continuing the Development of Stem Cells for Therapy in Hypoparathyroidism

Diane S. Krause, M.D., Ph.D.,Professor of Laboratory Medicine, of Cell Biology, and of Pathology 

Thyroid cancer occurs three times more often in women than men. Treatment often includes the removal of the thyroid gland, and a common, unavoidable complication of surgery to remove the malignancy is removal of the nearby parathyroid glands, which are critical for calcium balance in the body. Hypoparathyroidism, which results from defects in the parathyroid glands or their removal during surgery to remove a cancerous thyroid, is a devastating disease that primarily affects women. Because patients lack the ability to regulate calcium levels in their blood, they are at risk for irregular heartbeat, debilitating muscle cramps, seizures and other serious conditions. Treatment typically involves taking calcium, but this can prove very challenging over a long period. Dr. Krause’s team had received previous funding through a WHRY pilot grant to begin development of stem cells that can be transformed into parathyroid cells. This newer, ongoing project aims to continue the inducement of stem cells to develop into parathyroid cells that would secrete parathyroid hormone to maintain normal calcium balance. Cellular replacement could potentially offer a cure.

Development of Stem Cells for Therapy in Hypoparathyroidism

Julie Ann Sosa, M.D., Associate Professor of Surgery (Oncology)

The four parathyroid glands, located in the neck behind the thyroid, regulate levels of calcium in the body which is vital to maintaining bone health, heart rate and a variety of bodily functions. Hypoparathyroidism, which is more common in women than men, occurs when there is an inactivity of parathyroid hormone. This results when the parathyroid glands are deficient or must be removed or are injured when surgeons are removing a cancerous thyroid. Regardless of the cause, the resulting calcium imbalance can radically lower quality of life; and frequent oral calcium replacements, which can have significant adverse effects such as renal failure or kidney stones, often are necessary. Dr. Sosa (an endocrine surgeon), and her collaborator Dr. Diane Krause (an expert in the development of stem cells for biomedical uses) are aiming to induce human embryonic stem cells to develop into parathyroid cells that would replace the parathyroid hormone.

Highlighted Study Findings

In this ongoing project, the first challenge was to assemble the right team of skilled and experienced scientists working with embryonic stem cells to turn pre-implantation embryonic stem cells (primitive, undifferentiated cells derived from pre-implantation embryos, capable of dividing when cultured) into endodermal cells (which give rise to cells found in a number of systems, including the parathyroid glands). This has now been accomplished, and the team has shown that they can turn embryonic stem cells into endodermal cells. The next two steps that the team is working on include determining whether these endodermal cells can become parathyroid cells and, if so, whether the team’s genetic techniques can turn skin cells from patients with hypoparathyroidism into functioning parathyroid cells. The ultimate goal is to create parathyroid cells that can be implanted in patients to replace the loss of parathyroid function.

Pilot Project Study was funded in 2010, Dr. Sosa is now at Duke University, NC