In vitro differentiation of parathyroid cells from stem cells
Awardee: Michael Mannstadt, MD
Institution: Massachusetts General Hospital/Harvard University
Award Amount: $1,000,000
Funding Period: January 1, 2020 - December 31, 2021
Summary:
Parathyroid glands produce parathyroid hormone (PTH), which is necessary for regulating blood calcium and phosphate levels and maintaining bone health. Patients with insufficient parathyroid gland activity (hypoparathyroidism) can suffer from multiple symptoms caused by low blood calcium levels, including minor problems like muscle twitching or severe, life-threatening complications such as tetany and seizures. Conventional treatment with calcium and active vitamin D does not replace the functions of PTH and can lead to undesired long-term effects, such as kidney stones. PTH replacement therapy requires daily self-injections.
Currently, testing of serum calcium involves a visit to a clinical laboratory, a blood draw, and a delay while the patient waits for a report of their test results. This delays dose adjustment and leads to hyper- or hypocalcemia.
The long-term goal of this proposal is to offer a regenerative therapy for patients with hypoparathyroidism using mature parathyroid cells differentiated from human stem cells. With our collaborators from several institutions, including stem cell and developmental biologists, parathyroid surgeons, and specialists in microencapsulation of human stem cell-derived hormone-producing cells, we aim to define genetic mechanisms governing parathyroid cell fate specification during embryonic development. We will target critical pathways using small molecule activators and inhibitors to facilitate parathyroid cell fate specification. We will also test a novel microencapsulation technique for human parathyroid cells by transplantation in mice.