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

Abstract

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.

Human dental pulp stromal cell conditioned medium alters endothelial cell behavior

“…Although the number of nodes, meshes and tube length were higher in groups exposed to CM, the results were not significant. However, studies have previously reported that CM from different sources of MSCs or their side populations have the ability to promote tube formation [ 5 , 45 , 46 ], mostly through VEGF signaling that plays a pivotal role in EC sprouting and tubular network formation. This was evidenced by a reduction in the tubular perimeters after addition of VEGF and/or FGF neutralizing antibodies [ 10 ].…”

Stem cell‐based therapies for cardiac diseases: The critical role of angiogenic exosomes

“…65,66 Previously performed experimental studies have well-demonstrated the promoting impact of CPCs on neo-vessel formation in vitro and in vivo. 67,68 For instance, Dougherty et al showed that exosomes derived from human CPCs could significantly enhance the tube formation in bovine aortic endothelial cells (BAECs) under physoxia (5% O 2 ) as compared to those isolated from ECs cultured in 1 and 21% O 2…”

The chick embryo chorioallantoic membrane assay as a model for the study of angiogenesis

“…Unlike other in vivo models, such as the murine subcutaneous implant, CAM assay is minimally invasive to the chick embryo and hence, considered a refinement model for animal research (KUE et al, 2015). Many studies have used CAM to evaluate tissue repair including studies about osteogenesis (YAN et al, 2016), myocardial regeneration (FANTON et al, 2016) and even induction of angiogenesis using polymer-based constructs (KANCZLER et al, 2007). We also analyzed the acceptability of the CAM assay over the time (Fig 2a).…”