title: Stem cell therapy for arterial restenosis: potential parameters contributing to the success of bone marrow-derived mesenchymal stromal cells.
abstract: OBJECTIVE
  Restenosis is a complex and heterogeneous pathophysiological phenomenon occurring in patients submitted to revascularization procedures. Previous studies proved the antirestenotic properties of injected allogenic mesenchymal stromal cells (MSCs) in an experimental model of rat carotid (re)stenosis induced through arteriotomy. In this study we describe some of the effects subsequent to MSC treatment of rats submitted to carotid arteriotomy and possibly responsible for their antirestenotic effect.
  
  
  METHODS
  Rat MSCs were isolated from bone marrow, expanded in vitro and characterized. Subsequently, we evaluated the effects of MSC administration via tail vein at 3 and 7 days after carotid arteriotomy both in rat serum and in injured carotids, focusing on DNA oxidative damage (8-oxo-dG detection), cell proliferation index (BrdU incorporation assay), apoptotic index (TUNEL assay), the expression of inflammation- and proliferation-related genes (RT-PCR), the release of growth factors and of inflammation-related cytokines (antibody arrays and ELISA).
  
  
  RESULTS
  MSC administration induced a greater cell proliferation in carotids after arteriotomy, together with an increased level of VEGF in the serum and with the higher expression of VEGF mRNA in injured carotids. Serum analysis also revealed a decreased level of the pro-inflammatory cytokines CXCL1, CXCL5, L-Selectin, ICAM-1 and LIX, and of TIMP1 and SDF-1alpha in MSC-treated rats. The MSC immunomodulatory activity was confirmed by the decreased expression of TLR2 and TLR4 in injured carotids.
  
  
  CONCLUSIONS
  MSCs play an immunomodulatory paracrine role when injected in rats submitted to carotid arteriotomy, accompanied by the release of VEGF, possibly contributing to the accelerated repair of the injured vascular wall.
authors.affiliation: Department of Experimental Medicine, Second University of Naples, Naples, Italy.
authors.forename: Amalia
authors.initials: A
authors.lastname: Forte
authors.forename: Barbara
authors.initials: B
authors.lastname: Rinaldi
authors.forename: Loredana
authors.initials: L
authors.lastname: Sodano
authors.forename: Liberato
authors.initials: L
authors.lastname: Berrino
authors.forename: Francesco
authors.initials: F
authors.lastname: Rossi
authors.forename: Mauro
authors.initials: M
authors.lastname: Finicelli
authors.forename: Mario
authors.initials: M
authors.lastname: Grossi
authors.forename: Gilda
authors.initials: G
authors.lastname: Cobellis
authors.forename: Chiara
authors.initials: C
authors.lastname: Botti
authors.forename: Marisa
authors.initials: M
authors.lastname: De Feo
authors.forename: Pasquale
authors.initials: P
authors.lastname: Santè
authors.forename: Umberto
authors.initials: U
authors.lastname: Galderisi
authors.forename: Marilena
authors.initials: M
authors.lastname: Cipollaro
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D017209:Apoptosis; D001854:Bone Marrow Cells / Q000166:cytology; D002339:Carotid Arteries / Q000378:metabolism / Q000473:pathology; D020212:Carotid Artery Injuries / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D016893:Carotid Stenosis / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D002453:Cell Cycle; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000097:blood; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D051195:Toll-Like Receptor 2 / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; C495343:Tlr2 protein, rat; C495347:Tlr4 protein, rat; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine