The effects of progenitor and differentiated cells on ectopic calcification of engineered vascular tissues

被引:5
作者
Dayekh, Khalil [1 ]
Mequanint, Kibret [1 ,2 ]
机构
[1] Univ Western Ontario, Dept Chem & Biochem Engn, 1151 Richmond St, London, ON N6A 5B9, Canada
[2] Univ Western Ontario, Sch Biomed Engn, 1151 Richmond St, London, ON N6A 5B9, Canada
关键词
Ectopic calcification; Engineered vascular tissues; Disease model; Osteogenic genes; Smooth muscle cells; Progenitor cells; Vitamin K; SMOOTH-MUSCLE-CELLS; MODEL; ROLES; PIT-1; AORTA;
D O I
10.1016/j.actbio.2020.08.019
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
Ectopic vascular calcification associated with aging, diabetes mellitus, atherosclerosis, and chronic kidney disease is a considerable risk factor for cardiovascular events and death. Although vascular smooth muscle cells are primarily implicated in calcification, the role of progenitor cells is less known. In this study, we engineered tubular vascular tissues from embryonic multipotent mesenchymal progenitor cells either without differentiating or after differentiating them into smooth muscle cells and studied ectopic calcification through targeted gene analysis. Tissues derived from both differentiated and undifferentiated cells calcified in response to hyperphosphatemic inorganic phosphate (Pi) treatment suggesting that a single cell-type (progenitor cells or differentiated cells) may not be the sole cause of the process. We also demonstrated that Vitamin K, which is the matrix gla protein activator, had a protective role against calcification in engineered vascular tissues. Addition of partially-soluble elastin upregulated osteogenic marker genes suggesting a calcification process. Furthermore, partially-soluble elastin downregulated smooth muscle myosin heavy chain (Myh11) gene which is a late-stage differentiation marker. This latter point, in turn, suggests that SMC may be switching into a synthetic phenotype which is one feature of vascular calcification. Taken together, our approach presents a valuable tool to study ectopic calcification and associated gene expressions relevant to clinical therapeutic targets. (C) 2020 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:288 / 298
页数:11
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