112 ISSN 1990-519X, Cell and Tissue Biology, 2018, Vol. 12, No. 2, pp. 112–119. © Pleiades Publishing, Ltd., 2018. Original Russian Text © L.S. Litvinova, V.V. Shupletsova, O.G. Khaziakhmatova, K.A. Yurova, V.V. Malashchenko, E.S. Melashchenko, N.M. Todosenko, M.Yu. Khlusova, Yu.P. Sharkeev, E.G. Komarova, M.B. Sedelnikova, E.O. Shunkin, I.A. Khlusov, 2017, published in Tsitologiya, 2017, Vol. 59, No. 12, pp. 858–866. Behavioral Changes of Multipotent Mesenchymal Stromal Cells in Contact with Synthetic Calcium Phosphates in vitro L. S. Litvinova a, *, V. V. Shupletsova a , O. G. Khaziakhmatova a , K. A. Yurova a , V. V. Malashchenko a , E. S. Melashchenko a , N. M. Todosenko a , M. Yu. Khlusova b , Yu. P. Sharkeev c, d , E. G. Komarova d , M. B. Sedelnikova d , E. O. Shunkin a , and I. A. Khlusov a, e a Laboratory of Immunology and Cell Biotechnology, Immanuel Kant Baltic Federal University, Kaliningrad, 236041 Russia b Pathophysiology Department, Siberian State Medical University, Tomsk, 634050 Russia c Experimental Physics Department, Tomsk Polytechnic University, Tomsk, 634050 Russia d Institute of Strength Physics and Materials Science of the Siberian Branch of the Russian Academy of Sciences, Tomsk, 634055 Russia e Morphology and General Pathology Department, Siberian State Medical University, Tomsk, 634050 Russia *e-mail: larisalitvinova@yandex.ru Received July 7, 2017 Abstract—Migration, proliferation, and osteogenic differentiation of human adipose-derived (AD) multipo- tent mesenchymal stromal cells (MMSCs) during in vitro modeling of indirect contact with calcium phos- phate (CP) or nanoparticles of synthetic hydroxyapatite (HA) have been studied. The results were registered with electrode (real-time cell analysis, RTCA) or visual (Cell-IQ) systems of long-term observation of cell cultures. Bulk specimens were use in a Cell-IQ® v2 MLF device as pure titanium substrates (10 × 10 × 1 mm 3 ) covered by a CP relief (roughness index R a = 2.4–4.4 μm) bilateral coating that was prepared by the micr-arc method from an aqueous solution of orthophosphoric acid (20 wt %), calcium carbonate (9 wt %), and synthetic HA (6 wt %). HA crystallites (1 mg/mL) were fabricated by mechanochemical synthesis and served as an irritant in RTCA investigation. The Cell-IQ system identified a 3.5- to 10-fold decrease in cell number at the interface with CP coatings with differing roughness during 14-day cell culturing. After 21 days, it was accompanied by a weak reduction of MMSC antigen expression (CD73, CD90, and CD105) as opposed to an increase in MMSC osteogenic differentiation and intercellular-matrix mineralization. In turn, HA nanodispersion reduced the speed of MMSC migration by 1.5 times (P < 0.001) during 25-h RTCA recording, which simulated cell invasion through the microporous membrane (8-μm diameter). Inhibition of migration and cell division with increased osteogenic differentiation of MMSCs has been suggested to be a possible effect of biodegradation products of synthetic CP materials. Keywords: stromal cells of human adipose tissue, motility, trafficking, membrane markers, osteogenic differ- entiation, hydroxylapatite, calcium phosphate coating, microtopography DOI: 10.1134/S1990519X18020062 INTRODUCTION Real-time cell analysis (Atienza et al., 2006) and Cell-IQ (Meindl et al., 2013) are contemporary tools for noninvasive investigation and continuous cell monitoring. They allow real-time determination of the cell morphology and behavior (viability, migration adhesion, proliferation, differentiation, maturation) under normal conditions and after treatment with var- ious stimuli (pharmacological agents, biomolecules, viruses, etc.) (Teng et al., 2013). Multipotent mesenchymal stromal cells (MMSCs), which are able to migrate into inflamma- tion, regeneration, and tumor-growth foci and transfer pharmaceutical drugs, biological molecules, and nanoparticles (Lepik et al., 2016), have been widely used in different studies. However, only isolated works have been devoted so far to modeling and determining the behavior of MMSCs in real time (Moniri et al., 2015). The applicability of survey tools to cell interac- tion with extracellular-matrix components and artifi- cial-implant materials remains largely untapped (e.g., Ozturk et al., 2014). The bone–implant boundary is a critical link for reparative bone regeneration. A major approach to promoting osseointegration of implanted materials is the use of calcium-phosphate (CP) coating. Depend- Abbreviations: HA—hydroxyapatite, CP—calcium phosphate, MI—cell-migration index, AT—adipose tissue, MMSC—multi- potent mesenchymal stromal cell, EDTA—ethylenedi- aminetetraacetic acid, RTCA—real-time cell analysis.