Differentiation of precursors into parathyroid-like cells for treatment of hypoparathyroidism.

Abstract:

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.

journal_name

Surgery

journal_title

Surgery

authors

Woods Ignatoski KM,Bingham EL,Frome LK,Doherty GM

doi

10.1016/j.surg.2010.09.021

subject

Has Abstract

pub_date

2010-12-01 00:00:00

pages

1186-9; discussion 1189-90

issue

6

eissn

0039-6060

issn

1532-7361

pii

S0039-6060(10)00513-1

journal_volume

148

pub_type

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