title: Highly efficient endosomal labeling of progenitor and stem cells with large magnetic particles allows magnetic resonance imaging of single cells.
abstract: Tracking transplanted stem cells using magnetic resonance imaging (MRI) could offer biologic insight into homing and engraftment. Ultrasmall dextran-coated iron oxide particles have previously been developed for uptake into cells to allow MRI tracking. We describe a new application of much larger, micron-scale, iron oxide magnetic particles with enhanced MR susceptibility, which enables detection of single cells at resolutions that can be achieved in vivo. In addition, these larger particles possess a fluorophore for histologic confirmation of cell distribution. We demonstrate highly efficient, nontoxic, endosomal uptake of these particles into hematopoietic CD34+ cells and mesenchymal stem cells documented by confocal and electron microscopy. Labeled cells retain biologic activity with preservation of colony-forming ability and differentiation capacity. MRI studies could detect labeled CD34+ cells and mesenchymal stem cells (MSCs) at single cell resolution. This appears to be a promising tool for serial noninvasive monitoring of in vivo cell homing and localization using MRI.
authors.affiliation: Hematology Branch, Laboratory of Molecular Biology, Laboratory National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Hinds
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Hill
authors.forename: Erik M
authors.initials: EM
authors.lastname: Shapiro
authors.forename: Mikko O
authors.initials: MO
authors.lastname: Laukkanen
authors.forename: Alfonso C
authors.initials: AC
authors.lastname: Silva
authors.forename: Christian A
authors.initials: CA
authors.lastname: Combs
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Varney
authors.forename: Robert S
authors.initials: RS
authors.lastname: Balaban
authors.forename: Alan P
authors.initials: AP
authors.lastname: Koretsky
authors.forename: Cynthia E
authors.initials: CE
authors.lastname: Dunbar
mesh_terms: D000818:Animals; D018952:Antigens, CD34; D002454:Cell Differentiation; D002455:Cell Division; D011992:Endosomes / Q000378:metabolism*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000493:pharmacokinetics*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008648:Mesoderm / Q000166:cytology; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D010012:Osteogenesis; D010087:Oxides / Q000493:pharmacokinetics*; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D013552:Swine
chemical_list: D018952:Antigens, CD34; D010087:Oxides; C094094:carboxydextran-coated magnetic iron oxide particles; D007501:Iron