BOSTON -- A discovery made by investigators from Beth Israel Deaconess Medical Center (BIDMC) and the Boston University School of Medicine (BUSM) may help lead to the development of a cell-based regenerative therapy to restore thyroid function in patients with cancer who have had their thyroids surgically removed and children born with congenital hypothyroidism. The new findings are described in the Oct. 22 issue of Cell Stem Cell.
"This research represents an important step toward the goal of being able to better treat thyroid diseases and being able to permanently rescue thyroid function through the transplantation of a patient's own engineered pluripotent stem cells," explained co-corresponding author Anthony N. Hollenberg, MD, Chief of the Division of Endocrinology, Diabetes and Metabolism at BIDMC and Professor of Medicine at Harvard Medical School.
"Until now, we haven't fully understood the natural process that underlies early thyroid development," said co-corresponding author Darrell N. Kotton, MD, Director of the Center for Regenerative Medicine (CReM) at BUSM and Boston Medical Center and Professor of Medicine and Pathology at BUSM. "With this paper, we've identified the signaling pathways in thyroid cells that regulate their differentiation, the process by which unspecialized stem cells give rise to specialized cells during early fetal development."
After deciphering this natural differentiation process, the investigators duplicated it in the laboratory dish by adding a sequence of proteins, called growth factors, to the fluid bathing the stem cells. The team then used murine pluripotent stem cells to regenerate thyroid function in a murine model of hypothyroidism. Next, they adapted this method using induced pluripotent stem cells (iPSCs) engineered from children with congenital hypothyroidism, who are born with genetic defects that prevent their thyroids from fully developing.
Hypothyroidism results when the thyroid gland produces too little thyroid hormone, which impairs metabolism and can result in slowed heart rate, weight gain and chronic symptoms of feeling cold and tired with decreased mental acuity. Although drugs are available to replace thyroid function, with this new discovery, "we can now envision that thyroid function could be restored by transplanting patients' own thyroid cells," said Hollenberg and Kotton.
This study was made possible through the collaboration of multiple teams of investigators from across North America. In particular, the co-first authors and co-senior authors worked together closely for several years. The two teams came together in the pursuit of new knowledge and patient-oriented treatments; they became close friends as they struggled to support each other through the tragic loss of co-first author, Anita Kurmann, MD, who died this summer in a biking accident.
Anita A. Kurmann of BIDMC and the Center for Regenerative Medicine, BU and BMC and Maria Serra of the Center for Regenerative Medicine, BU and BMC were co-lead authors of this study.
Other coauthors include BU investigators Finn Hawkins, Munemasa Mori, Jyh C. Jean, and Laertis Ikonomou; BIDMC investigators Inna Astapova, and Soumya Ullas; Cincinnati Children's Hospital investigators Scott A. Rankin, Aaron Zorn, and John M. Shannon; Melanie Bilodeau and Janet Rossant of The Hospital for Sick Children, Toronto; and Robin R. Deterding of the Unviersity of Colorado Denver.
Funding for this study was provided by the Swiss National Science Foundation (SNSF) PBBS P3-146612, L.I. by R01 HL111574 and an award co-sponsored by the chILD Foundation/American Thoracic Society, M.B. by a postdoctoral fellowships from CIHR/Canadian Lung Association/GSK partnership and from the FRQS, A.M.Z. by R01 HL114898, and D.N.K. by R01 HL095993, R01 HL108678, R01 HL122442, and U01HL110-967.
About Beth Israel Deaconess Medical Center
Beth Israel Deaconess Medical Center is a patient care, teaching and research affiliate of Harvard Medical School and consistently ranks as a national leader among independent hospitals in National Institutes of Health funding.
BIDMC is in the community with Beth Israel Deaconess Hospital-Milton, Beth Israel Deaconess Hospital-Needham, Beth Israel Deaconess Hospital-Plymouth, Anna Jaques Hospital, Cambridge Health Alliance, Lawrence General Hospital, Signature Healthcare, Beth Israel Deaconess HealthCare, Community Care Alliance and Atrius Health. BIDMC is also clinically affiliated with the Joslin Diabetes Center and Hebrew Rehabilitation Center and is a research partner of Dana-Farber/Harvard Cancer Center and The Jackson Laboratory. BIDMC is the official hospital of the Boston Red Sox. For more information, visit http://www.
About Boston University School of Medicine
Originally established in 1848 as the New England Female Medical College, and incorporated into Boston University in 1873, Boston University School of Medicine today is a leading academic medical center with an enrollment of more than 700 medical students and 950 students pursuing degrees in graduate medical sciences. BUSM received $167 million in funding in FY2014 for research in amyloidosis, arthritis, cardiovascular disease, cancer, infectious diseases, pulmonary disease and dermatology, among others. The School's teaching affiliates include Boston Medical Center, its primary teaching hospital, the VA Healthcare System in Boston, Roger Williams Medical Center in Rhode Island, as well as Boston HealthNet, a network of 15 community health centers.