title: In vitro angiogenic performance and in vivo brain targeting of magnetized endothelial progenitor cells for neurorepair therapies.
abstract: Endothelial progenitor cells (EPCs) represent a promising approach for cell-based therapies to induce tissue repair; however, their effective delivery into the brain has remained a challenge. We loaded EPCs with superparamagnetic iron oxide nanoparticles (SPIONs), assessed their angiogenic potential and evaluated their guidance to the brain using an external magnet. SPIONs were stored in the cytoplasm within endosomes/lysosomes as observed by transmission electron microscopy (TEM) and could be visualized as hypointense signals by magnetic resonance imaging (MRI) T2-weighted images. In vitro SPION-loaded EPCs were fully functional, forming vessel-like structures in Matrigel®, and displayed enhanced migration and secretion of growth factors (VEGF and FGF), which was associated with a moderate increase in reactive oxygen species production. Furthermore, in vivo MRI of treated mice showed accumulated hypointense signals consistent with SPION-loaded EPCs engraftment. Thus, we demonstrate that loading EPCs with SPIONs represents a safe and effective strategy for precise cell guidance into specific brain areas.
  
  
  BACKGROUND
  This study investigates the potential role of endothelial progenitor cells in neuro-repair strategies of the central nervous system using SPION-loaded EPCs and magnetic guidance to the target organ. The authors demonstrate ex vivo cellular viability and maintained function following SPION load as well as successful guidance of the EPCs to the target site via MR imaging in a murine model.
authors.affiliation: Institut de Ciència de Materials de Barcelona, Consejo Superior de Investigaciones Científicas (ICMAB-CSIC), Campus de la UAB, Bellaterra, Catalunya, Spain.
authors.forename: Elisa
authors.initials: E
authors.lastname: Carenza
authors.affiliation: Neurovascular Research Laboratory and Neurovascular Unit, Vall d'Hebron Institut de Recerca, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Passeig Vall d'Hebron 119-129, Barcelona, Catalunya, Spain.
authors.forename: Verónica
authors.initials: V
authors.lastname: Barceló
authors.affiliation: Neurovascular Research Laboratory and Neurovascular Unit, Vall d'Hebron Institut de Recerca, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Passeig Vall d'Hebron 119-129, Barcelona, Catalunya, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Morancho
authors.affiliation: Institut de Ciència de Materials de Barcelona, Consejo Superior de Investigaciones Científicas (ICMAB-CSIC), Campus de la UAB, Bellaterra, Catalunya, Spain.
authors.forename: Lisa
authors.initials: L
authors.lastname: Levander
authors.affiliation: Neurovascular Research Laboratory and Neurovascular Unit, Vall d'Hebron Institut de Recerca, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Passeig Vall d'Hebron 119-129, Barcelona, Catalunya, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Boada
authors.affiliation: Institut de Ciència de Materials de Barcelona, Consejo Superior de Investigaciones Científicas (ICMAB-CSIC), Campus de la UAB, Bellaterra, Catalunya, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Laromaine
authors.affiliation: Institut de Ciència de Materials de Barcelona, Consejo Superior de Investigaciones Científicas (ICMAB-CSIC), Campus de la UAB, Bellaterra, Catalunya, Spain. Electronic address: roig@icmab.es.
authors.forename: Anna
authors.initials: A
authors.lastname: Roig
authors.affiliation: Neurovascular Research Laboratory and Neurovascular Unit, Vall d'Hebron Institut de Recerca, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Passeig Vall d'Hebron 119-129, Barcelona, Catalunya, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Montaner
authors.affiliation: Neurovascular Research Laboratory and Neurovascular Unit, Vall d'Hebron Institut de Recerca, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Passeig Vall d'Hebron 119-129, Barcelona, Catalunya, Spain. Electronic address: anna.rosell@vhir.org.
authors.forename: Anna
authors.initials: A
authors.lastname: Rosell
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D005290:Ferric Compounds / Q000008:administration & dosage*; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D051379:Mice; D046529:Microscopy, Electron, Transmission; D011859:Radiography; D017382:Reactive Oxygen Species / Q000378:metabolism; D013194:Staining and Labeling; D013234:Stem Cells / Q000187:drug effects* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
chemical_list: D005290:Ferric Compounds; D058185:Magnetite Nanoparticles; D017382:Reactive Oxygen Species; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; C000499:ferric oxide
keywords: Angiogenesis; Endothelial progenitor cell; Growth factor; Iron oxide nanoparticle; MRI; Magnetic field guidance