Researchers from the Center for Regenerative Medicine (CReM) and the Department of Medicine at Boston Medical Center (BMC) and Boston University (BU) have made a breakthrough that holds promise for developing new therapies to treat hypothyroidism, a condition where the thyroid gland does not produce enough hormones. The research team, led by Darrell Kotton, MD, and Anthony Hollenberg, MD, developed a successful protocol for producing mature thyroid follicular epithelial cells (TFCs), which are responsible for making thyroid hormones. The TFCs the researchers developed can be transplanted into thyroid-deficient animal models, according to a new study in Stem Cell Reports . These cells could someday help boost thyroid hormone in human patients and relieve hypothyroidism symptoms like fatigue, muscle issues, depression, memory problems, and a slowed heart rate.
The researchers derived TFCs from human induced pluripotent stem cells (iPSCs), which originate from the donated skin or blood cells of adults and, with the reactivation of four genes that regulate development, are reprogrammed back to an embryonic stem cell-like state. iPSC cells can then be differentiated toward any cell type in the body.
"Induced pluripotent stem cells offer a powerful tool for regenerative medicine because they provide an unlimited source of patient-specific cells that can potentially be used to treat a range of diseases," says Dr. Kotton, founding director of the CReM, a joint effort between BMC and BU, and David C. Seldin Professor of Medicine at BU Chobanian and Avedesian School of Medicine. "This study brings us one step closer to using iPSC-derived thyroid cells for cell-based therapies in hypothyroidism."
First, the team developed human iPSCs that glow when exposed to a specific wavelength of light if they have the thyroid-specific genes NKX2-1 and PAX8. This allowed for precise identification and purification of cells destined to become TFCs. The researchers then induced the development of TFCs through a carefully optimized differentiation protocol using serum-free media and key signaling molecules, BMP4 and FGF2. Single-cell RNA sequencing confirmed that the majority of iPSCs successfully differentiated into mature TFCs within one month, with the ability to organize into three-dimensional thyroid follicles.
When the team transplanted TFCs into a thyroid-deficient animal model, the cells formed thyroid-like structures, including thyroglobulin-positive follicles that are necessary for proper thyroid function.
"Our findings offer a significant advancement in the ability to generate human thyroid cells in the lab. While further work is needed before this can become a clinical therapy, the protocol we've developed could pave the way for regenerative treatments for hypothyroidism," says Dr. Hollenberg, president of BMC and Professor of Medicine at the school. "One day, we hope to offer a cell-based solution for patients who undergo thyroid surgery or are born with congenital hypothyroidism."
