Researchers from Beth Israel Deaconness Medical Center (BIDMC), in collaboration with the Boston University School of Medicine (BUSM), have made a breakthrough in cell-based regenerative therapy that may one day restore thyroid function in human patients using their own cells. Their results are published in the October issue of Cell Stem Cell

About 4.6 percent of the U.S. population age 12 and older has hypothyroidism, in which the thyroid gland does not produce enough thyroid hormone. Its causes range from congenital issues to thyroid cancers. People with the condition must take synthetic thyroid medication. Until recently, researchers did not fully understand the natural process of early thyroid development, which hindered the development of new treatments. The new study reveals this process. 

“It turns out that once the embryo starts to develop its layers, when it makes its endoderm cells, there is a cell fate decision to either become lung or thyroid cells,” study senior co-author Anthony Hollenberg tells mental_floss. He and Darrell Kotton, director of the Center for Regenerative Medicine (CReM) dreamed up the study together at a social engagement. The researchers already knew of a host of proteins known as growth factors involved in the signaling pathways as the cells differentiate to become lung and thyroid cells, but they needed to narrow it down.

“Through a subtraction approach, our researchers figured out that just two of the growth factors were required for thyroid formation,” says Hollenberg, chief of endocrinology, diabetes, and metabolism at BIDMC and professor of medicine at Harvard Medical School.

With more collaborators at the University of Cincinnati, they were able to identify these same two growth factors regulating thyroid cell specification in mice models, the commonly used frog model Xenopus, and in humans.

Next, they took mouse stem cells called fibroblasts and reprogrammed them to become stem cells, resulting in induced pluripotent stem cells. They converted these into thyroid cells, then transplanted them into mice whose thyroids had been removed. “Sure enough, they functioned as thyroids,” Hollenberg says. This hacked thyroid function worked for the duration of the mice’s lives, about eight months, leading the researchers to theorize that the stem cell transplant regenerates thyroid function.

They were able to replicate the results in mice using human cells. This time they transplanted human pluripotent stem cells derived from children born with congenital hypothyroidism. Once again the cells took on the thyroid function.

This research has positive implications for people who take thyroid hormone replacement medications. “The vast majority of people on these medications feel great, but many would prefer to have their own tissue,” Hollenberg says. But while future treatments based on this research could potentially replace pills for some, they would not be able to help with many people who have Hashimoto’s disease, an autoimmune condition where the immune system attacks its own thyroid cells: “We’d have to figure out ways to encapsulate the cells to prevent them from being attacked by the immune system."

The next step in the research, Hollenberg says, is to “perfect the protocol so we can implant the human cells into mice and show they work. Then we could think about getting this ready for giving it to humans.”