Darrell Kotton and his research team from Beth Deaconess Medical Center, in collaboration with researchers from the Boston University School of Medicine have devised a workable protocol for differentiating Human pluripotent stem cells into functional thyroid gland cells.
Every year, many people are diagnosed with an underactive thyroid and many others lose their thyroid as a result of thyroid cancer. Designing treatments that can help replace lost thyroid tissue would certainly be a welcome thing for these patients.
By working with mouse embryonic stem cells, Kotton and his colleagues showed that two growth factors, BMP4 and FGF2, and induce foregut endodermal cells to differentiate into thyroid cells. This simple signaling pathway not only efficiently generates thyroid tissue from endoderm, but this pathway turns out to be commonly used in species as diverse as frogs, mice and humans.
The BMP4/FGF2-treated foregut cells differentiated into small thyroid organics that Kotton and his team were able to transplant into thyroid-deficient mice. These transplantations restored normal thyroid function to these mice.
While mice cells are a fine model system for human diseases, they are not exactly the same. Can this procedure work with human cells? To answer that question, Kotton and his coworkers used human induced pluripotent stem cells (iPSCs) and subjected them to the same BMP4/FGF2 protocol after they had first differentiated the cells into endoderm. In addition, Kotton and his team made thyroid cells from iPSCs derived from cells taken from patients with a specific type of hypothyroidism (interactive thyroid). These patients lack a gene called NKX2-1, and suffer from congenital hypothyroidism.
The thyroid is responsible for your basal metabolic rate. Hypothyroidism or an interactive thyroid can cause patients to gain weight, feel tired constantly, have trouble concentrating, and have a slow heart rate. Hypothyroidism is usually treated with synthetic thyroid hormones that are taken orally. However, restoring a patient’s own thyroid tissue or even replacing defective thyroid tissue with repaired thyroid tissue would be a huge boon to thyroid patients.
This work has discovered the regulatory mechanisms that drive the establishment of the thyroid. It also provides a significant step toward cell-based regenerative therapy for hypothyroidism and the replacement of the thyroid after thyroid cancer treatments.
These results were published in the journal Cell Stem Cell, October 2015 DOI:10.1016/j.stem.2015.09.004.