Cardiac atrial appendage stem cells promote angiogenesis in vitro and in vivo.
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.
Laboratory of Experimental Hematology, Jessa Hospital, Hasselt, Belgium; Faculty of Medicine and Life Sciences, Hasselt University, Hasselt, Belgium. Electronic address: yanick.fanton@uhasselt.be.
Yanick
Y
Fanton
Faculty of Medicine and Life Sciences, Hasselt University, Hasselt, Belgium.
Cynthia
C
Houbrechts
Laboratory of Experimental Hematology, Jessa Hospital, Hasselt, Belgium; Faculty of Medicine and Life Sciences, Hasselt University, Hasselt, Belgium.
Leen
L
Willems
Laboratory of Experimental Hematology, Jessa Hospital, Hasselt, Belgium.
Annick
A
Daniëls
AC Biobanking, University Hospital Leuven, Leuven, Belgium.
Loes
L
Linsen
Biomedical Research Institute, Hasselt University, Hasselt, Belgium.
Jessica
J
Ratajczak
Biomedical Research Institute, Hasselt University, Hasselt, Belgium.
Annelies
A
Bronckaers
Biomedical Research Institute, Hasselt University, Hasselt, Belgium.
Ivo
I
Lambrichts
Laboratory of Experimental Hematology, Jessa Hospital, Hasselt, Belgium; Faculty of Medicine and Life Sciences, Hasselt University, Hasselt, Belgium.
Jeroen
J
Declercq
Laboratory of Experimental Hematology, Jessa Hospital, Hasselt, Belgium; Faculty of Medicine and Life Sciences, Hasselt University, Hasselt, Belgium.
Jean-Luc
JL
Rummens
Faculty of Medicine and Life Sciences, Hasselt University, Hasselt, Belgium; Department of Cardiothoracic Surgery, Jessa Hospital, Hasselt, Belgium.
Marc
M
Hendrikx
Laboratory of Experimental Hematology, Jessa Hospital, Hasselt, Belgium; Faculty of Medicine and Life Sciences, Hasselt University, Hasselt, Belgium.
Karen
K
Hensen
D043925:Angiogenesis Inducing Agents / Q000378:metabolism; D000818:Animals; D020517:Atrial Appendage / Q000166:cytology*; D015415:Biomarkers; D002478:Cells, Cultured; D002642:Chick Embryo; D017077:Culture Media, Conditioned / Q000494:pharmacology; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D019332:Endothelin-1 / Q000378:metabolism; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism; D018919:Neovascularization, Physiologic; D040901:Proteomics / Q000379:methods; D013234:Stem Cells / Q000378:metabolism*; D046888:Tissue Array Analysis; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D043925:Angiogenesis Inducing Agents; D015415:Biomarkers; D017077:Culture Media, Conditioned; D019332:Endothelin-1; D018972:Insulin-Like Growth Factor Binding Protein 3; D042461:Vascular Endothelial Growth Factor A
Angiogenesis; Cardiac progenitor cells; Endothelial cell; Growth factors and cytokines; Stem cell