title: An in vitro model of mesenchymal stem cell targeting using magnetic particle labelling.
abstract: The specific targeting of cells to sites of tissue damage in vivo is a major challenge precluding the success of stem cell-based therapies. Magnetic particle-based targeting may provide a solution. Our aim was to provide a model system to study the trapping and potential targeting of human mesenchymal stem cells (MSCs) during in vitro fluid flow, which ultimately will inform cell targeting in vivo. In this system magnet arrays were used to trap superparamagnetic iron oxide particle-doped MSCs. The in vitro experiments demonstrated successful cell trapping, where the volume of cells trapped increased with magnetic particle concentration and decreased with increasing flow rate. Analysis of gene expression revealed significant increases in COL1A2 and SOX9. Using principles established in vitro, a proof-of-concept in vivo experiment demonstrated that magnetic particle-doped, luciferase-expressing MSCs were trapped by an implanted magnet in a subcutaneous wound model in nude mice. Our results demonstrate the effectiveness of using an in vitro model for testing superparamagnetic iron oxide particles to develop successful MSC targeting strategies during fluid flow, which ultimately can be translated to in vivo targeted delivery of cells via the circulation in a variety of tissue-repair models.
authors.affiliation: Institute for Science and Technology in Medicine, Guy Hilton Research Centre, Keele University, UK.
authors.forename: Alicia J
authors.initials: AJ
authors.lastname: El Haj
authors.affiliation: Institute for Science and Technology in Medicine, Guy Hilton Research Centre, Keele University, UK.
authors.forename: John R
authors.initials: JR
authors.lastname: Glossop
authors.affiliation: Institute for Science and Technology in Medicine, Guy Hilton Research Centre, Keele University, UK.
authors.forename: Harpal S
authors.initials: HS
authors.lastname: Sura
authors.affiliation: Department of Physics, University of Warwick, Coventry, UK.
authors.forename: Martin R
authors.initials: MR
authors.lastname: Lees
authors.affiliation: Institute for Science and Technology in Medicine, Guy Hilton Research Centre, Keele University, UK.
authors.forename: Bin
authors.initials: B
authors.lastname: Hu
authors.affiliation: Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Vienna, Austria.|Austrian Cluster for Tissue Regeneration, Vienna, Austria.
authors.forename: Susanne
authors.initials: S
authors.lastname: Wolbank
authors.affiliation: Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Vienna, Austria.|Austrian Cluster for Tissue Regeneration, Vienna, Austria.
authors.forename: Martijn
authors.initials: M
authors.lastname: van Griensven
authors.affiliation: Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Vienna, Austria.|Austrian Cluster for Tissue Regeneration, Vienna, Austria.
authors.forename: Heinz
authors.initials: H
authors.lastname: Redl
authors.affiliation: Institute for Science and Technology in Medicine, Guy Hilton Research Centre, Keele University, UK.|J. Crayton Pruitt Family Department of Biomedical Engineering and Department of Materials Science and Engineering, University of Florida, Gainesville, FL, USA.
authors.forename: Jon
authors.initials: J
authors.lastname: Dobson
mesh_terms: D000273:Adipose Tissue / Q000166:cytology; D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D020219:Chondrogenesis / Q000235:genetics; D003911:Dextrans / Q000378:metabolism*; D004705:Endocytosis; D005786:Gene Expression Regulation; D006801:Humans; D008163:Luminescent Measurements; D060328:Magnetic Phenomena; D058185:Magnetite Nanoparticles; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D008954:Models, Biological; D010012:Osteogenesis / Q000235:genetics; D012212:Rheology; D013194:Staining and Labeling
chemical_list: D015415:Biomarkers; D003911:Dextrans; D058185:Magnetite Nanoparticles; C065507:ferumoxides
keywords: adult stem cells; experimental models; in vivo optical imaging; in vivo tracking; stem cell targeting; stem cell transplantation