Litvinova Larisa S, Khaziakhmatova Olga G, Shupletsova Valeria V, Yurova Kristina A, Malashchenko Vladimir V, Shunkin Egor O, Ivanov Pavel A, Komarova Ekaterina G, Chebodaeva Valentina V, Porokhova Ekaterina D, Gereng Elena A, Khlusov Igor A
Center for Immunology and Cell Biotechnology, Immanuel Kant Baltic Federal University, 236029 Kaliningrad, Russia.
Laboratory of Physics of Nanostructured Biocomposites, Institute of Strength Physics and Materials Science SB RAS, 634055 Tomsk, Russia.
Materials (Basel). 2020 Sep 27;13(19):4307. doi: 10.3390/ma13194307.
Calcium phosphate (CaP) materials are among the best bone graft substitutes, but their use in the repair of damaged bone in tumor patients is still unclear. The human Jurkat T lymphoblast leukemia-derived cell line (Jurkat T cells) was exposed in vitro to a titanium (Ti) substrate (10 × 10 × 1 mm) with a bilateral rough (average roughness index () = 2-5 μm) CaP coating applied via the microarc oxidation (MAO) technique, and the morphofunctional response of the cells was studied. Scanning electron microscopy (SEM), X-ray diffraction (XRD), and energy dispersive X-ray spectroscope (EDX) analyses showed voltage-dependent (150-300 V) growth of structural ( index, mass, and thickness) and morphological surface and volume elements, a low Ca/P ratio (0.3-0.6), and the appearance of crystalline phases of CaHPO (monetite) and β-CaPO (calcium pyrophosphate). Cell and molecular reactions in 2-day and 14-day cultures differed strongly and correlated with the values. There was significant upregulation of expression (1.7-fold), IL-17 secretion, the presentation of the activation antigens CD25 (by 2.7%) and CD95 (by 5.15%) on CD4 cells, and 1.5-2-fold increased cell apoptosis and necrosis after two days of culture. Hyperactivation-dependent death of CD4 cells triggered by the surface roughness of the CaP coating was proposed. Conversely, a 3.2-fold downregulation in expression increased the percentages of CD4 cells and their CD95 subset (by 15.5% and 22.9%, respectively) and inhibited the secretion of 17 of 27 test cytokines/chemokines without a reduction in Jurkat T cell survival after 14 days of coculture. Thereafter, cell hypoergy and the selection of an independent viable CD4 subset of tumor cells were proposed. The possible role of negative zeta potentials and Ca as effectors of CaP roughness was discussed. The continuous (2-14 days) 1.5-6-fold reductions in the secretion of vascular endothelial growth factor (VEGF) by tumor cells correlated with the values of microarc CaP-coated Ti substrates seems to limit surgical stress-induced metastasis of lymphoid malignancies.
磷酸钙(CaP)材料是最佳的骨移植替代物之一,但其在肿瘤患者受损骨修复中的应用仍不明确。将人Jurkat T淋巴母细胞白血病衍生细胞系(Jurkat T细胞)在体外暴露于通过微弧氧化(MAO)技术施加双侧粗糙(平均粗糙度指数()= 2 - 5μm)CaP涂层的钛(Ti)基材(10×10×1mm),并研究细胞的形态功能反应。扫描电子显微镜(SEM)、X射线衍射(XRD)和能量色散X射线光谱仪(EDX)分析表明,结构(指数、质量和厚度)以及形态表面和体积元素的生长与电压相关(150 - 300V),Ca/P比值较低(0.3 - 0.6),并且出现了CaHPO(磷酸氢钙)和β-CaPO(焦磷酸钙)的晶相。2天和14天培养中的细胞和分子反应差异很大,且与值相关。培养两天后,表达显著上调(1.7倍)、IL-17分泌增加、CD4细胞上活化抗原CD25(增加2.7%)和CD95(增加5.15%)的表达增加,细胞凋亡和坏死增加1.5 - 2倍。有人提出,由CaP涂层的表面粗糙度引发的CD4细胞过度活化依赖性死亡。相反,培养14天后,表达下调3.2倍增加了CD4细胞及其CD95亚群的百分比(分别增加15.5%和22.9%),并抑制了27种测试细胞因子/趋化因子中17种的分泌,而Jurkat T细胞存活率未降低。此后,有人提出细胞功能减退以及肿瘤细胞独立存活的CD4亚群的选择。讨论了负zeta电位和Ca作为CaP粗糙度效应器的可能作用。肿瘤细胞分泌血管内皮生长因子(VEGF)持续(2 - 14天)降低1.5 - 6倍,这与微弧CaP涂层Ti基材的值相关,似乎限制了手术应激诱导的淋巴恶性肿瘤转移。