Background
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.
Methods
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.
Results
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.
Conclusion
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.
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Article info
Publication history
Accepted:
September 16,
2010
Identification
Copyright
© 2010 Mosby, Inc. Published by Elsevier Inc. All rights reserved.
