As stem cell researchers make progress in regenerative therapies for the eye, heart, and brain, those working on a less studied part of the anatomy, the thyroid gland, have quietly been amassing the biological knowledge of thyroid development needed to make a leap of their own. In a study published in Cell Stem Cell, Boston-led researchers present the first stem-cell-derived human thyroid tissue generated from both normal individuals and patients with hypothyroidism.
Previous work in the field had demonstrated that mouse thyroid cells could be generated from embryonic stem cells but only by artificially over-expressing key thyroid-specific genes. "We found this process could be recapitulated in a laboratory dish by adding a sequence of proteins called growth factors to the fluid bathing the stem cells," says co-senior author Darrell Kotton of the Center for Regenerative Medicine of Boston University and Boston Medical Center.
Credit: Anita Kurmann and Maria Serra
The investigators tested their method - which relied mainly on the growth factors FGF2 and BMP4 - with mouse pluripotent stem cells, which were then used to regenerate thyroid function after transplantation in a mouse model of hypothyroidism. The team then adapted the method to produce thyroid cells using induced pluripotent stem cells generated from children who had genetic defects that had caused them to have an underactive thyroid.
"Hypothyroidism is common in adults and also affects children born with congenital or inherited forms of thyroid disease," says co-senior author Anthony Hollenberg of Beth Israel Deaconess Medical Center. "Although there are good drugs available to replace thyroid function, we can now envision that children or adults may one day be able to receive sustained rescue of their thyroid function by transplanting their own thyroid cells regenerated in the laboratory from cells made by reprogramming their skin or blood cells."
The advance also offers a model of thyroid development and growth that can be used to study the biology of thyroid diseases, including thyroid cancer.