title: Endocardial tip cells in the human embryo - facts and hypotheses.
abstract: Experimental studies regarding coronary embryogenesis suggest that the endocardium is a source of endothelial cells for the myocardial networks. As this was not previously documented in human embryos, we aimed to study whether or not endothelial tip cells could be correlated with endocardial-dependent mechanisms of sprouting angiogenesis. Six human embryos (43-56 days) were obtained and processed in accordance with ethical regulations; immunohistochemistry was performed for CD105 (endoglin), CD31, CD34, α-smooth muscle actin, desmin and vimentin antibodies. Primitive main vessels were found deriving from both the sinus venosus and aorta, and were sought to be the primordia of the venous and arterial ends of cardiac microcirculation. Subepicardial vessels were found branching into the outer ventricular myocardium, with a pattern of recruiting α-SMA+/desmin+ vascular smooth muscle cells and pericytes. Endothelial sprouts were guided by CD31+/CD34+/CD105+/vimentin+ endothelial tip cells. Within the inner myocardium, we found endothelial networks rooted from endocardium, guided by filopodia-projecting CD31+/CD34+/CD105+/ vimentin+ endocardial tip cells. The myocardial microcirculatory bed in the atria was mostly originated from endocardium, as well. Nevertheless, endocardial tip cells were also found in cardiac cushions, but they were not related to cushion endothelial networks. A general anatomical pattern of cardiac microvascular embryogenesis was thus hypothesized; the arterial and venous ends being linked, respectively, to the aorta and sinus venosus. Further elongation of the vessels may be related to the epicardium and subepicardial stroma and the intramyocardial network, depending on either endothelial and endocardial filopodia-guided tip cells in ventricles, or mostly on endocardium, in atria.
authors.affiliation: Division of Anatomy, Faculty of Dental Medicine, "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania; MEDCENTER-Center of Excellence in Laboratory Medicine and Pathology, Bucharest, Romania.
authors.forename: Mugurel C
authors.initials: MC
authors.lastname: Rusu
authors.affiliation: Department of Obstetrics and Gynaecology "Dr.I.Cantacuzino" Hospital, "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania.
authors.forename: Cristian V
authors.initials: CV
authors.lastname: Poalelungi
authors.affiliation: Division of Anatomy, Faculty of Dental Medicine, "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania.
authors.forename: Alexandra D
authors.initials: AD
authors.lastname: Vrapciu
authors.affiliation: Division of Histology and Cytology, Faculty of Dental Medicine, "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania; Laboratory of Molecular Medicine, "Victor Babeş" National Institute of Pathology, Bucharest, Romania.
authors.forename: Mihnea I
authors.initials: MI
authors.lastname: Nicolescu
authors.affiliation: Division of Legal Medicine and Bioethics, Department 2 Morphological Sciences, Faculty of Medicine, "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania.
authors.forename: Sorin
authors.initials: S
authors.lastname: Hostiuc
authors.affiliation: Research Center for Microscopic Morphology and Immunology, Department of Morphology, University of Medicine and Pharmacy of Craiova, Craiova, Romania.
authors.forename: Laurentiu
authors.initials: L
authors.lastname: Mogoanta
authors.affiliation: Division of Anatomy, Faculty of Medicine, "Gr.T.Popa" University of Medicine and Pharmacy, Iasi, Romania.
authors.forename: Traian
authors.initials: T
authors.lastname: Taranu
mesh_terms: D004622:Embryo, Mammalian / Q000166:cytology*; D047108:Embryonic Development; D004699:Endocardium / Q000166:cytology / Q000196:embryology*; D006801:Humans; D009206:Myocardium / Q000166:cytology