Osteogenic potential of adipose mesenchymal stem cells is not correlated with aortic valve calcification


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.


stem cells, calcification of aortic valve, osteogenic differentiation


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Boström, K. I. 2016. Where do we stand on vascular calcification? Vascular pharmacology 84:8–14. https://doi.org/10.1016/j.vph.2016.05.014

Boström, K. I., Rajamannan, N. M. and Towler, D. A. 2011. The regulation of valvular and vascular sclerosis by osteogenic morphogens. Circulation research 109(5):564–577. https://doi.org/10.1161/CIRCRESAHA.110.234278

Demer, L. L. and Tintut, Y. 2014. Inflammatory, metabolic, and genetic mechanisms of vascular calcification. Arteriosclerosis, thrombosis, and vascular biology 34(4):715–723. https://doi.org/10.1161/ATVBAHA.113.302070

Dmitrieva, R. I., Revittser, A. V., Klukina, M. A., Sviryaev, Y. V., Korostovtseva, L. S., Kostareva, A. A., Zaritskey, A. Y. and Shlyakhto, E. V. 2015. Functional properties of bone marrow derived multipotent mesenchymal stromal cells are altered in heart failure patients, and could be corrected by adjustment of expansion strategies. Aging (Albany NY) 7(1):14–25. https://doi.org/10.18632/aging.100716

Farrington-Rock, C., Crofts, N., Doherty, M., Ashton, B., Griffin-Jones, C. and Canfield, A. 2004. Chondrogenic and adipogenic potential of microvascular pericytes. Circulation 110(15):2226–2232. https://doi.org/10.1161/01.CIR.0000144457.55518.E5

Fernandez, M., Simon, V., Herrera, G., Cao, C., Favero, H. and Minguell, J. 1997. Detection of stromal cells in peripheral blood progenitor cell collections from breast cancer patients. Bone marrow transplantation 20(4):265–271. https://doi.org/10.1038/sj.bmt.1700890

Furukawa, K.-I. 2014. Recent advances in research on human aortic valve calcification. Journal of pharmacological sciences 124(2):129–137. https://doi.org/10.1254/jphs.13R05CR

Gössl, M., Khosla, S., Zhang, X., Higano, N., Jordan, K. L., Loeffler, D., Enriquez-Sarano, M., Lennon, R. J., Lerman, L. O. and Lerman, A. 2012. Role of circulating osteogenic progenitor cells in calcific aortic stenosis. Journal of the American College of Cardiology 60(19):1945–1953. https://doi.org/10.1016/j.jacc.2012.07.042

Huss, R., Lange, C., Weissinger, E. M., Kolb, H. J. and Thalmeier, K. 2000. Evidence of peripheral blood-derived, plastic-adherent CD34−/low hematopoietic stem cell clones with mesenchymal stem cell characteristics. Stem cells 18(4):252–260. https://doi.org/10.1634/stemcells.18-4-252

Kostina, A., Shishkova, A., Ignatieva, E., Irtyuga, O., Bogdanova, M., Levchuk, K., Golovkin, A., Zhiduleva, E., Uspenskiy, V. and Moiseeva, O. 2018. Different Notch signaling in cells from calcified bicuspid and tricuspid aortic valves. Journal of Molecular and Cellular Cardiology 114:211–219. https://doi.org/10.1016/j.yjmcc.2017.11.009

Kuznetsov, S. A., Mankani, M. H., Gronthos, S., Satomura, K., Bianco, P. and Robey, P. G. 2001. Circulating skeletal stem cells. The Journal of cell biology 153(5):1133–1140. https://doi.org/10.1083/jcb.153.5.1133

Leszczynska, A. and Murphy, J. M. 2018. Vascular calcification: Is it rather a stem/progenitor cells driven phenomenon? Frontiers in bioengineering and biotechnology 6:10. https://doi.org/10.3389/fbioe.2018.00010

Liu, X. and Xu, Z. 2016. Osteogenesis in calcified aortic valve disease: from histopathological observation towards molecular understanding. Progress in biophysics and molecular biology 122(2):156–161. https://doi.org/10.1016/j.pbiomolbio.2016.02.002

Malashicheva, A., Bogdanova, M., Zabirnyk, A., Smolina, N., Ignatieva, E., Freilikhman, O., Fedorov, A., Dmitrieva, R., Sjöberg, G. and Sejersen, T. 2015. Various lamin A/C mutations alter expression profile of mesenchymal stem cells in mutation specific manner. Molecular genetics and metabolism 115(2):118–127. https://doi.org/10.1016/j.ymgme.2015.04.006

Mathieu, P., Boulanger, M.-C. and Bouchareb, R. 2014. Molecular biology of calcific aortic valve disease: towards new pharmacological therapies. Expert review of cardiovascular therapy 12(7):851–862. https://doi.org/10.1586/14779072.2014.923756

Nomura, A., Seya, K., Yu, Z., Daitoku, K., Motomura, S., Murakami, M., Fukuda, I. and Furukawa, K.-I. 2013. CD34-negative mesenchymal stem-like cells may act as the cellular origin of human aortic valve calcification. Biochemical and biophysical research communications 440(4):780–785. https://doi.org/10.1016/j.bbrc.2013.10.003

Otsuru, S., Tamai, K., Yamazaki, T., Yoshikawa, H. and Kaneda, Y. 2007. Bone marrow-derived osteoblast progenitor cells in circulating blood contribute to ectopic bone formation in mice. Biochemical and biophysical research communications 354(2):453–458. https://doi.org/10.1016/j.bbrc.2006.12.226

Pal, S. N. and Golledge, J. 2010. Osteo-Progenitors in Vascular Calcification. Journal of atherosclerosis and thrombosis 18(7):551–559. https://doi.org/10.5551/jat.8656

Rabkin-Aikawa, E., Farber, M., Aikawa, M. and Schoen, F. J. 2004. Dynamic and reversible changes of interstitial cell phenotype during remodeling of cardiac valves. Journal of Heart Valve Disease 13(5):841–847

Rochefort, G. Y., Delorme, B., Lopez, A., Herault, O., Bonnet, P., Charbord, P., Eder, V. and Domenech, J. 2006. Multipotential mesenchymal stem cells are mobilized into peripheral blood by hypoxia. Stem cells 24(10):2202–2208. https://doi.org/10.1634/stemcells.2006-0164

Rutkovskiy, A., Malashicheva, A., Sullivan, G., Bogdanova, M., Kostareva, A., Stenslokken, K. O., Fiane, A. and Vaage, J. 2017. Valve interstitial cells: The key to understanding the pathophysiology of heart valve calcification. Journal of American Heart Association 6(9):e006339. https://doi.org/10.1161/jaha.117.006339

Speer, M. Y., Yang, H.-Y., Brabb, T., Leaf, E., Look, A., Lin, W.-L., Frutkin, A., Dichek, D. and Giachelli, C. M. 2009. Smooth muscle cells give rise to osteochondrogenic precursors and chondrocytes in calcifying arteries. Circulation research 104(6):733–741. https://doi.org/10.1161/CIRCRESAHA.108.183053

Tintut, Y., Alfonso, Z., Saini, T., Radcliff, K., Watson, K., Boström, K. and Demer, L. L. 2003. Multilineage potential of cells from the artery wall. Circulation 108(20):2505–2510. https://doi.org/10.1161/01.CIR.0000096485.64373.C5

Wang, W., Li, C., Pang, L., Shi, C., Guo, F., Chen, A., Cao, X. and Wan, M. 2014. Mesenchymal stem cells recruited by active TGFβ contribute to osteogenic vascular calcification. Stem cells and development 23(12):1392–1404. https://doi.org/10.1089/scd.2013.0528

Zuk, P. A., Zhu, M., Mizuno, H., Huang, J., Futrell, J. W., Katz, A. J., Benhaim, P., Lorenz, H. P. and Hedrick, M. H. 2001. Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue engineering 7(2):211–228. https://doi.org/10.1089/107632701300062859

Zvaifler, N. J., Marinova-Mutafchieva, L., Adams, G., Edwards, C. J., Moss, J., Burger, J. A. and Maini, R. N. 2000. Mesenchymal precursor cells in the blood of normal individuals. Arthritis Research and Therapy 2(6):477. https://doi.org/10.1186/ar130
How to Cite
Malashicheva, A., Irtyuga, O., Kostina, A., Ignatieva, E., Zhiduleva, E., Semenova, D., Golovkin, A., Gordeev, M., Moiseeva, O., & Kostareva, A. (2018). Osteogenic potential of adipose mesenchymal stem cells is not correlated with aortic valve calcification. Biological Communications, 63(2), 117–122. https://doi.org/10.21638/spbu03.2018.204
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