Cardiac atrial appendage stem cells promote angiogenesis in vitro and in vivo

被引:21
作者
Fanton, Yanick [1 ,2 ]
Houbrechts, Cynthia [2 ]
Willems, Leen [1 ,2 ]
Daniels, Annick [1 ]
Linsen, Loes [3 ]
Ratajczak, Jessica [4 ]
Bronckaers, Annelies [4 ]
Lambrichts, Ivo [4 ]
Declercq, Jeroen [1 ,2 ]
Rummens, Jean-Luc [1 ,2 ]
Hendrikx, Marc [2 ,5 ]
Hensen, Karen [1 ,2 ]
机构
[1] Jessa Hosp, Lab Expt Hematol, Hasselt, Belgium
[2] Hasselt Univ, Fac Med & Life Sci, Hasselt, Belgium
[3] Univ Hosp Leuven, AC Biobanking, Leuven, Belgium
[4] Hasselt Univ, Biomed Res Inst, Hasselt, Belgium
[5] Jessa Hosp, Dept Cardiothorac Surg, Hasselt, Belgium
基金
比利时弗兰德研究基金会;
关键词
Angiogenesis; Growth factors and cytokines; Stem cell; Cardiac progenitor cells; Endothelial cell; CARDIOSPHERE-DERIVED CELLS; THERAPEUTIC MYOCARDIAL ANGIOGENESIS; EMBRYO CHORIOALLANTOIC MEMBRANE; ENDOTHELIAL PROGENITOR CELLS; STROMAL CELLS; PARACRINE MECHANISMS; HEART-FAILURE; REPAIR; ADULT; MIGRATION;
D O I
10.1016/j.yjmcc.2016.06.005
中图分类号
R5 [内科学];
学科分类号
100201 [内科学];
摘要
Cardiac atrial appendage stem cells (CASCs) show extraordinary myocardial differentiation properties, making them ideal candidates for myocardial regeneration. However, since the myocardium is a highly vascularized tissue, revascularization of the ischemic infarct area is essential for functional repair. Therefore, this study assessed if CASCs contribute to cardiac angiogenesis via paracrine mechanisms. First, it was demonstrated that CASCs produce and secrete high levels of numerous angiogenic growth factors, including vascular endothelial growth factor (VEGF), endothelin-1 (ET-1) and insulin-like growth factor binding protein 3 (IGFBP-3). Functional in vitro assays with a human microvascular endothelial cell line (HMEC-1) and CASC CM showed that CASCs promote endothelial cell proliferation, migration and tube formation, the most important steps of the angiogenesis process. Addition of inhibitory antibodies against identified growth factors could significantly reduce these effects, indicating their importance in CASC-induced neovascularization. The angiogenic potential of CASCs and CASC CM was also confirmed in a chorioallantoic membrane assay, demonstrating that CASCs promote blood vessel formation in vivo. In conclusion, this study shows that CASCs not only induce myocardial repair by cardiomyogenic differentiation, but also stimulate blood vessel formation by paracrine mechanisms. The angiogenic properties of CASCs further strengthen their therapeutic potential and make them an optimal stem cell source for the treatment of ischemic heart disease. (C) 2016 Elsevier Ltd. All rights reserved.
引用
收藏
页码:235 / 244
页数:10
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