title: Non-viral magnetic engineering of endothelial cells with microRNA and plasmid-DNA-An optimized targeting approach.
abstract: Genetic modulation of angiogenesis is a powerful tool for the treatment of multiple disorders. Here, we describe a strategy to produce modified endothelial cells, which can be efficiently magnetically guided. First, we defined optimal transfection conditions with both plasmid and microRNA, using a polyethyleneimine/magnetic nanoparticle-based vector (PEI/MNP), previously designed in our group. Further, two approaches were assessed in vitro: direct vector guidance and magnetic targeting of transfected cells. Due to its higher efficiency, including simulated dynamic conditions, production of miR/PEI/MNP-modified magnetically responsive cells was selected for further detailed investigation. In particular, we have studied internalization of transfection complexes, functional capacities and intercellular communication of engineered cells and delivery of therapeutic miR. Moreover, we demonstrated that 104miRNA/PEI/MNP-modified magnetically responsive cells loaded with 0.37pg iron/cell are detectable with MRI. Taken together, our in vitro findings show that PEI/MNP is highly promising as a multifunctional tool for magnetically guided angiogenesis regulation.
authors.affiliation: Reference and Translation Center for Cardiac Stem Cell Therapy (RTC), Department of Cardiac Surgery, University of Rostock, Rostock, Germany. Electronic address: natalia.voronina@med.uni-rostock.de.
authors.forename: Natalia
authors.initials: N
authors.lastname: Voronina
authors.affiliation: Reference and Translation Center for Cardiac Stem Cell Therapy (RTC), Department of Cardiac Surgery, University of Rostock, Rostock, Germany. Electronic address: heiko.lemcke@uni-rostock.de.
authors.forename: Heiko
authors.initials: H
authors.lastname: Lemcke
authors.affiliation: Physikalisch-Technische Bundesanstalt, Berlin, Germany. Electronic address: Frank.Wiekhorst@ptb.de.
authors.forename: Frank
authors.initials: F
authors.lastname: Wiekhorst
authors.affiliation: Department of Radiology and Neuroradiology, Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany;. Electronic address: kuehn@uni-greifswald.de.
authors.forename: Jens-Peter
authors.initials: JP
authors.lastname: Kühn
authors.affiliation: Reference and Translation Center for Cardiac Stem Cell Therapy (RTC), Department of Cardiac Surgery, University of Rostock, Rostock, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Rimmbach
authors.affiliation: Reference and Translation Center for Cardiac Stem Cell Therapy (RTC), Department of Cardiac Surgery, University of Rostock, Rostock, Germany. Electronic address: gustav.steinhoff@med.uni-rostock.de.
authors.forename: Gustav
authors.initials: G
authors.lastname: Steinhoff
authors.affiliation: Reference and Translation Center for Cardiac Stem Cell Therapy (RTC), Department of Cardiac Surgery, University of Rostock, Rostock, Germany. Electronic address: davidrob@med.uni-rostock.de.
authors.forename: Robert
authors.initials: R
authors.lastname: David
mesh_terms: D004247:DNA; D042783:Endothelial Cells; D008280:Magnetics; D035683:MicroRNAs; D036103:Nanotechnology / Q000379:methods; D009389:Neovascularization, Pathologic; D010957:Plasmids; D011094:Polyethyleneimine; D014162:Transfection
chemical_list: D035683:MicroRNAs; D011094:Polyethyleneimine; D004247:DNA
keywords: Cell engineering; MRI; Magnetic nanoparticles; Magnetic targeting; Non-viral delivery; microRNA