Hypoparathyroidism is the most frequent permanent complication of thyroid surgery. Our hypothesis is that human precursor cells in culture can be differentiated into parathyroid cells and used to reconstitute function. Human embryonic stem cells (hESCs) are a stable model to study differentiation into parathyroid-like cells. In prior work, the BG01-hESC line was stimulated to form parathyroid-like cells. This cell line is no longer available, however, and additional studies were needed to confirm and extend prior observations.
Increasing concentrations of fetal bovine serum and timed exposure to Activin A were used to differentiate H1-hESC into parathyroid-like cells. The potential benefit of Sonic hedgehog exposure on parathyroid-like cell development also was evaluated by serial alterations of culture conditions. Calcium-sensing receptor (CaSR), GCM2, and PTH expression (RT-PCR) and PTH protein secretion (ELISA) were used as markers of differentiated cells.
We successfully modified our prior protocol to generate cells that express CaSR, GCM2, and PTH RNA from undifferentiated H1-hESC. The cells also secreted PTH.
We replicated parathyroid differentiation using H1-hESC cells. Our data advance the project toward in vitro differentiation of precursor cells isolated from individual patients for autotransplantation.
To read this article in full you will need to make a payment
Purchase one-time access:Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
One-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:Subscribe to Surgery
Already a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
Scott-Coombs D, Kinsman R. Second National Audit Report. In: British Association of Endocrine Surgeons, editors. Parathyroid: outcomes, Vol. 1. Oxfordshire, UK: Henley-on-Thames; 2007. p. 110-2.
- Complications of thyroid and parathyroid surgery.in: Mulholland M.W. Doherty G.M. Complications in surgery. Lippincott, Williams & Wilkins, Philadelphia2006
- Dynamic and structural properties of the skeleton in hypoparathyroidism.J Bone Miner Res. 2008; 23: 2018-2024
- Differentiation of hES cells to a parathyroid-like phenotype.Stem Cell Develop. 2009; 18: 1071-1080
- Doherty G.M. Skogseid B.M. Surgical endocrinology. Lippincott, Williams & Wilkins, Philadelphia2001
- Parathyroid autotransplantation during thyroidectomy. Results of long-term follow-up.Ann Surg. 1996; 223 ([See comment]) (discussion 478-480): 472-478
- Parathyroid autotransplantation during thyroidectomy.ANZ J Surg. 2002; 72 ([See comment]): 902-907
- Transplantation of the parathyroid glands in man: clinical indications and results.Surgery. 1975; 78: 34-44
Accepted: September 16, 2010
© 2010 Mosby, Inc. Published by Elsevier Inc. All rights reserved.