Differentiation of Human Adipose-Derived Stem Cells into Parathyroid Hormone-Secreting Cells

Introduction: Complications arising from neck surgery are the most common causes of acquired hypoparathyroidism. Parathyroid hormone (PTH) regulates serum calcium and vitamin D levels. The current treatments for hypoparathyroidism, including PTH supplements and high doses of calcium and vitamin D, are a life-long burden and may cause side effects. Recent studies have shown that parathyroid gland differentiation occurs from embryonic stem cells, thymic epithelial cells, and tonsil-derived stem cells. Because adipose-derived stem cells (ADSCs) do not face ethical concerns raised for studies with human embryonic stem cells, in the present study, we attempted to induce differentiation of ADSCs into parathyroid cells. Methods: ADSCs were isolated from abdominal subcutaneous adipose tissues obtained by plastic surgery from three male donors (mean age, 40 years). For differentiation into parathyroid-like cells, ADSCs were incubated in minimum essential medium-alpha supplemented with activin A and soluble Sonic hedgehog for 7–21 d. The parathyroid differentiation markers PTH , glial cells missing homolog 2 ( GCM2 ), and chemokine (C-C motif) ligand 21 ( CCL21 ) were detected using real-time quantitative polymerase chain reaction to confirm differentiation. Results: The ADSCs exhibited flat and vacuolated morphology, which changed into secretory parathyroid gland–like nodules on day 21 after differentiation. The mRNA expression of PTH, GCM2, and CCL21 increased in the differentiated cells. Furthermore, a significant amount of PTH protein was detected in differentiated cells on day 7 post-differentiation. Conclusion: Human ADSCs isolated from adipose tissues successfully differentiated into PTH-secreting cells. ADSC-secreted PTH may be a promising therapeutic for hypoparathyroidism patients.