title: Endothelial juxtaposition of distinct adult stem cells activates angiogenesis signaling molecules in endothelial cells.
abstract: Efficacy of therapeutic angiogenesis needs a comprehensive understanding of endothelial cell (EC) function and biological factors and cells that interplay with ECs. Stem cells are considered the key components of pro- and anti-angiogenic milieu in a wide variety of physiopathological states, and interactions of EC-stem cells have been the subject of controversy in recent years. In this study, the potential effects of three tissue-specific adult stem cells, namely rat marrow-derived mesenchymal stem cells (rBMSCs), rat adipose-derived stem cells (rADSCs) and rat muscle-derived satellite cells (rSCs), on the endothelial activation of key angiogenic signaling molecules, including VEGF, Ang-2, VEGFR-2, Tie-2, and Tie2-pho, were investigated. Human umbilical vein endothelial cells (HUVECs) and rat lung microvascular endothelial cells (RLMECs) were cocultured with the stem cells or incubated with the stem cell-derived conditioned media on Matrigel. Following HUVEC-stem cell coculture, CD31-positive ECs were flow sorted and subjected to western blotting to analyze potential changes in the expression of the pro-angiogenic signaling molecules. Elongation and co-alignment of the stem cells were seen along the EC tubes in the EC-stem cell cocultures on Matrigel, with cell-to-cell dye communication in the EC-rBMSC cocultures. Moreover, rBMSCs and rADSCs significantly improved endothelial tubulogenesis in both juxtacrine and paracrine manners. These two latter stem cells dynamically up-regulated VEGF, Ang-2, VREGR-2, and Tie-2 but down-regulated Tie2-pho and the Tie2-pho/Tie-2 ratio in HUVECs. Induction of pro-angiogenic signaling in ECs by marrow- and adipose-derived MSCs further indicates the significance of stem cell milieu in angiogenesis dynamics.
authors.affiliation: Department of Clinical Pathology, Faculty of Veterinary Medicine, University of Tehran, P.O Box: 14155-6453, Qareeb St., Azadi Ave., Tehran, Iran.
authors.forename: Elham
authors.initials: E
authors.lastname: Mohammadi
authors.affiliation: Department of Clinical Pathology, Faculty of Veterinary Medicine, University of Tehran, P.O Box: 14155-6453, Qareeb St., Azadi Ave., Tehran, Iran. nasirim@ut.ac.ir.
authors.forename: Seyed Mahdi
authors.initials: SM
authors.lastname: Nassiri
authors.affiliation: Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Reza
authors.initials: R
authors.lastname: Rahbarghazi
authors.affiliation: Department of Biology, Faculty of Sciences, University of Guilan, Rasht, Iran.
authors.forename: Vahid
authors.initials: V
authors.lastname: Siavashi
authors.affiliation: Faculty of Veterinary Medicine, Amol University of Special Modern Technologies, Amol, Iran.
authors.forename: Atefeh
authors.initials: A
authors.lastname: Araghi
mesh_terms: D000273:Adipose Tissue / Q000166:cytology; D000328:Adult; D053687:Adult Stem Cells / Q000166:cytology*; D042702:Angiopoietin-2 / Q000378:metabolism; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000494:pharmacology; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D008168:Lung / Q000166:cytology; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects; D055806:Microvessels / Q000166:cytology; D018919:Neovascularization, Physiologic / Q000187:drug effects; D009928:Organ Specificity / Q000187:drug effects; D017208:Rats, Wistar; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D042702:Angiopoietin-2; D017077:Culture Media, Conditioned; D042461:Vascular Endothelial Growth Factor A
keywords: Angiogenesis; Coculture; Endothelial cell; Signaling; Stem cell