A novel approach for the production of parathyroid-like cells from stem cells — cells from which all others with specialized functions are generated — could help find new treatments for hypoparathyroidism, a study suggests.
The study, “Differentiation of parathyroid hormone expressing cells from human pluripotent stem cells,” led by scientists at Yale University, was published in the journal Endocrinology.
Hypoparathyroidism is characterized by abnormally low levels of parathyroid hormone (PTH), which is normally produced in the parathyroid glands, located in the neck. The parathyroid hormone regulates calcium levels in the blood, helping to prevent bone destruction and increase the formation of new bone.
Treatment complications and a lack of efficacy in a substantial number of patients with calcium and active vitamin D supplements led to the development of an engineered form of PTH. That engineered PTH, called Natpara, by Shire, is a hormone replacement therapy for people with hypoparathyroidism.
Yet, limitations — such as the burdensome daily injections and the short duration of effects — mean that other approaches are needed.
Pluripotent stem cells are able to differentiate, or grow and turn into, all types of body tissue. However, getting stem cells to differentiate into other cell types usually requires orchestrated molecular cues, to mimic processes that normally happen during development.
“The development of a protocol that reliably generates parathyroid-like cells from pluripotent stem cells would allow for the production of an unlimited number of parathyroid cells for biological studies, pharmaceutical drug screening, and other cell therapeutic options,” the scientists wrote.
Here, the researchers described such a protocol, which involves a multi-step process over 37 days with signaling proteins and other molecules, as well as the stimulation of PTH secretion.
To determine whether the cells were “parathyroid-like,” the team analyzed gene expression, meaning which genes are “off” or “on.” The results showed that the generated cells had gene expression profiles similar to what would be expected in true parathyroid cells. Importantly, this included the production of PTH.
Specifically, the protocol led to parathyroid-like cells from two different types of stem cells: human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSC). As their names suggest, hESCs are found in human embryos, while iPSCs are stem cells that have been “reverse-engineered” from other cell types, such as skin cells.
Notably, the successful production of PTH-producing cells was accomplished in two separate labs.
“A major obstacle for this type of research is demonstrating the ability to reproduce the technique in other laboratories,” Diane Krause, MD, PhD, the study’s senior author and associate director of the Yale Stem Cell Center, said in a press release.
“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,” Krause said. Colleagues from the University of California, San Francisco provided additional critical assistance.
The new protocol may give researchers a new model with which to study the parathyroid glands. In addition, this type of technology could create a foundation for the development of new therapies for hypoparathyroidism.
“We anticipate that this protocol will facilitate further identification of the biological determinants of PTH expression and secretion, and will serve as a useful resource for development of additional treatment options for patients with parathyroid-related conditions,” the researchers concluded.
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