title: Labeling of mesenchymal stromal cells with iron oxide-poly(L-lactide) nanoparticles for magnetic resonance imaging: uptake, persistence, effects on cellular function and magnetic resonance imaging properties.
abstract: OBJECTIVE
  Mesenchymal stromal cells (MSC) are the focus of research in regenerative medicine aiming at the regulatory approval of these cells for specific indications. To cope with the regulatory requirements for somatic cell therapy, novel approaches that do not interfere with the natural behavior of the cells are necessary. In this context in vivo magnetic resonance imaging (MRI) of labeled MSC could be an appropriate tool. Cell labeling for MRI with a variety of different iron oxide preparations is frequently published. However, most publications lack a comprehensive assessment of the non-interference of the contrast agent with the functionality of the labeled MSC, which is a prerequisite for the validity of cell-tracking via MRI.
  
  
  METHODS
  We studied the effects of iron oxide-poly(l-lactide) nanoparticles in MSC with flow cytometry, transmission electron microscopy (TEM), confocal laser scanning microscopy (CLSM), Prussian blue staining, CyQuant® proliferation testing, colony-forming unit-fibroblast (CFU-F) assays, flow chamber adhesion testing, immunologic tests and differentiation tests. Furthermore iron-labeled MSC were studied by MRI in agarose phantoms and Wistar rats.
  
  
  RESULTS
  It could be demonstrated that MSC show rapid uptake of nanoparticles and long-lasting intracellular persistence in the endosomal compartment. Labeling of the MSC with these particles has no influence on viability, differentiation, clonogenicity, proliferation, adhesion, phenotype and immunosuppressive properties. They show excellent MRI properties in agarose phantoms and after subcutaneous implantation in rats over several weeks.
  
  
  CONCLUSIONS
  These particles qualify for studying MSC homing and trafficking via MRI.
authors.affiliation: DRK Blood Service Baden-Württemberg-Hessia, Institute for Clinical Transfusion Medicine and Immunogenetics Ulm and Institute of Transfusion Medicine, University of Ulm, Ulm, Germany.
authors.forename: Gerlinde
authors.initials: G
authors.lastname: Schmidtke-Schrezenmeier
authors.forename: Markus
authors.initials: M
authors.lastname: Urban
authors.forename: Anna
authors.initials: A
authors.lastname: Musyanovych
authors.forename: Volker
authors.initials: V
authors.lastname: Mailänder
authors.forename: Markus
authors.initials: M
authors.lastname: Rojewski
authors.forename: Natalie
authors.initials: N
authors.lastname: Fekete
authors.forename: Cedric
authors.initials: C
authors.lastname: Menard
authors.forename: Erika
authors.initials: E
authors.lastname: Deak
authors.forename: Karin
authors.initials: K
authors.lastname: Tarte
authors.forename: Volker
authors.initials: V
authors.lastname: Rasche
authors.forename: Katharina
authors.initials: K
authors.lastname: Landfester
authors.forename: Hubert
authors.initials: H
authors.lastname: Schrezenmeier
mesh_terms: D000818:Animals; D004146:Dioxanes / Q000737:chemistry; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism*; D005240:Feasibility Studies; D005290:Ferric Compounds / Q000737:chemistry; D006801:Humans; D007279:Injections, Subcutaneous; D008279:Magnetic Resonance Imaging; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D053758:Nanoparticles / Q000737:chemistry / Q000627:therapeutic use*; D011859:Radiography; D051381:Rats; D017208:Rats, Wistar; D013194:Staining and Labeling / Q000379:methods; D033581:Stem Cell Transplantation
chemical_list: D004146:Dioxanes; D005290:Ferric Compounds; C000499:ferric oxide; C091880:dilactide