title: Effects of bone marrow mesenchymal stem cells (BM-MSCs) on rat pial microvascular remodeling after transient middle cerebral artery occlusion.
abstract: Previous studies have shown that the pial microcirculation remodeling improves neurological outcome after middle cerebral artery occlusion (MCAO), accompanied by higher expression of vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS), modulating in vivo angiogenesis. This study was aimed to assess the effects of bone marrow mesenchymal stem cells (BM-MSCs) infused after MCAO on rat pial microcirculation. Animals were subjected to 2 h MCAO followed by BM-MSCs infusion into internal carotid artery. Pial microcirculation was observed at different reperfusion times by fluorescence microscopy. Geometric characteristics of arteriolar networks, permeability increase, leukocyte adhesion, perfused capillary density, VEGF, and endothelial nitric oxide synthase (e-NOS) expression were evaluated. Green fluorescent protein (GFP)-BM-MSCs were used to evaluate their distribution and cell phenotype development during reperfusion. BM-MSCs stimulated a geometric rearrangement of pial networks with formation of new anastomotic vessels sprouting from preexistent arterioles in the penumbra at 7-14-28 days of reperfusion. At the same time VEGF and eNOS expression increased. GFP-BM-MSCs appear to be involved in endothelial and smooth muscle cell programming in the infarcted area. In conclusion, transient MCAO induced pial vascular remodeling characterized by arteriolar anastomotic arcades (originated from preexistent arterioles in penumbra area) able to overlap the ischemic core supplying blood to the neuronal tissue. BM-MSCs appear to accelerate angiogenic processes facilitating new vessel formation; this mechanism was promoted by an increase in VEGF and eNOS expression.
authors.affiliation: Department of Clinical Medicine and Surgery, "Federico II" University Medical School Naples, Italy.
authors.forename: Dominga
authors.initials: D
authors.lastname: Lapi
authors.affiliation: Rheumatology Unit, Department of Internal Medicine, University of Pisa Pisa, Italy.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Vagnani
authors.affiliation: Department of Clinical Medicine and Surgery, "Federico II" University Medical School Naples, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Sapio
authors.affiliation: Department of Clinical Medicine and Surgery, "Federico II" University Medical School Naples, Italy.
authors.forename: Teresa
authors.initials: T
authors.lastname: Mastantuono
authors.affiliation: Department of Neuroscience, Reproductive and Odontostomatologic Sciences, "Federico II" University Medical School Naples, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Boscia
authors.affiliation: Department of Neuroscience, Reproductive and Odontostomatologic Sciences, "Federico II" University Medical School Naples, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pignataro
authors.affiliation: Department of Clinical and Biological Sciences, University of Torino Orbassano, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Penna
authors.affiliation: Department of Clinical and Biological Sciences, University of Torino Orbassano, Italy.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Pagliaro
authors.affiliation: Department of Clinical Medicine and Surgery, "Federico II" University Medical School Naples, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Colantuoni
keywords: angiogenesis; bone marrow mesenchymal stem cells; cerebral microcirculation; endothelium-derived factors; stroke