Abstract
Osteogenic transformation as a result of cellular plasticity could be both beneficial, in the case of bone formation, and hazardous, in the case of vascular calcification. Mechanisms driving vascular calcification remain poorly understood, while calcification of the vessels is one of the leading causes of morbidity and mortality. In particular, calcification of the aortic valve is a serious complication requiring surgical intervention. The mechanisms behind aortic valve calcification and the origin of cells driving osteogenic transformation of the aortic valve remain questionable. A circulating stem cell theory supports the view that pathologic calcification could originate not only from valve cells, but also from other sources. The aim of this study was to estimate the osteogenic potential of adipose tissue-derived mesenchymal stem cells (MSCs) from people with calcification of the aortic valve versus MSCs from healthy people; further, to compare the capacity of osteogenic differentiation between MSCs and valve interstitial cells (VICs) from healthy donors and patients with severe calcification of the aortic valve. MSCs and VICs were isolated from either healthy donors or from patients with aortic valve calcification. The cells were immunophenotyped for conventional MSC markers by flow cytometry. Osteogenic differentiation was induced by addition of specific osteogenic inductors to the culture medium. Osteogenic differentiation was assessed by alizarin red staining and by estimation of RUNX2 expression by qPCR. The MSCs of healthy donors were capable of efficient osteogenic differentiation, while MSCs of the patients with aortic valve calcification were not capable of osteogenic differentiation. We conclude that there is no correlation between the capacity of adipose MSCs to osteogenically transform and calcification of the aortic valve. Most likely, peripheral MSCs of adipose origin could not be a source of aortic valve calcification.
Highlights
The formation of bone tissue and pathological calcification of the tissues of the heart and vessels have similar signs
We have recently shown that valve interstitial cells (VICs) of patients with Calcific aortic valve disease (CAVD) are more susceptible to proosteogenic induction and more readily undergo osteogenic differentiation compared to VICs from normal healthy valves (Kostina et al, 2018)
VICs from the patients with calcific aortic disease were isolated from explanted aortic valves in the course of surgical intervention, and mesenchymal stem cells (MSCs) from the same patients were isolated from subcutaneous adipose tissue
Summary
The formation of bone tissue and pathological calcification of the tissues of the heart and vessels have similar signs. The trigger mechanisms that lead to abnormal calcification of the heart and vessels remain largely unexplored. Vascular calcification is a frequent cardiovascular complication accompanying aging and various pathologies (Demer and Tintut, 2014). Other studies have demonstrated that mesenchymal-derived progenitor cells in the vessel wall could be involved in vascular calcification (Tintut et al, 2003; Farrington-Rock et al, 2004)
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