Stromal Stem Cells from Parathyroid Glands of Patients with Secondary Hyperparathyroidism Demonstrate Higher Telomerase Activity and Osteogenic Differentiation Ability than Normal Bone Marrow Derived Stromal Stem Cells

Abstract

Aims: The aim of this study was to isolate and extensively characterize parathyroid gland stem cells (PT-SCs) from secondary hyperparathyroidism cases. For this purpose, proliferation capacity, phenotypic properties, differentiation characteristics and gene expression profiles were analyzed and compared with mesenchymal stem cells from bone marrow (BM-MSCs) of the human. Methods: Stem cells isolated from PT and BM were analyzed by flow cytometry, RT-PCR, Real Time-PCR, and immunocytochemistry. Both cell lines were directionally differentiated towards adipogenic, osteogenic and neurogenic cell lineages. Results: The isolated hPT-SCs share similar characteristics of hBM-MSCs by immunophenotypic, histological and molecular analyses. Both cells were shown to differentiate successfully into adipogenic and osteogenic cell lines. Embryonic stem cell markers Pou5F1, Zpf42, FoxD3, Sox2 and Nanog were also expressed beside 5 fold higher telomerase activity in hPT-SCs that could indicate the regenerative ability of the human parathyroid gland. The osteogenic cell markers were expressed by hPT-SCs, which transformed efficiently into osteogenic cell lines, both at the level of genes (BMP2, BMP4, BGLAP, Coll11a1, Runx2, Sparc) and of proteins (BMP2, BMP4, Osteocalcin, Osteonectin, Osteopontin). Higher alkaline phosphatase (ALP) activity indicating osteogenic differentiation was determined in hPT-SCs from secondary hyperparathyroidism patients. Conclusion: PT-SCs might responsible for the calcified parathyroid glands and other ectopic calcifications including the vascular ones, observed in the secondary hyperparathyroidism cases, beside parathyroid hormone-dependent hypercalcemia leading diffusion of calcium phosphate precipitation in tissues.