title: Evaluation of intracellular labeling with micron-sized particles of iron oxide (MPIOs) as a general tool for in vitro and in vivo tracking of human stem and progenitor cells.
abstract: Magnetic resonance imaging (MRI)-based tracking is increasingly attracting attention as a means of better understanding stem cell dynamics in vivo. Intracellular labeling with micrometer-sized particles of iron oxide (MPIOs) provides a practical MRI-based approach due to superior detectability  relative to smaller iron oxide particles. However, insufficient information is available about the general utility across cell types and the effects on cell vitality of MPIO labeling of human stem cells. We labeled six human cell types from different sources: mesenchymal stem cells derived  from bone marrow (MSCs), mesenchymal stem cells derived from adipose tissue (ASCs), presumptive adult neural stem cells (ad-NSCs), fetal neural progenitor cells (f-NPCs), a glioma cell line (U87), and glioblastoma tumor stem cells (GSCs), with two different sizes of MPIOs (0.9 and 2.84 µm).  Labeling and uptake efficiencies were highly variable among cell types. Several parameters of general cell function were tested in vitro. Only minor differences were found between labeled and unlabeled cells with respect to proliferation rate, mitotic duration, random motility, and capacity  for differentiation to specific phenotypes. In vivo behavior was tested in chicken embryos and severe combined immunodeficient (SCID) mice. Postmortem histology showed that labeled cells survived and could integrate into various tissues. MRI-based tracking over several weeks in the SCID mice  showed that labeled GSCs and f-NPCs injected into the brain exhibited translocations similar to those seen for unlabeled cells and as expected from migratory behavior described in previous studies. The results support MPIO-based cell tracking as a generally useful tool for studies of human  stem cell dynamics in vivo.
authors.affiliation: Department of Physiology, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Boulland
authors.forename: Doreen S Y
authors.initials: DS
authors.lastname: Leung
authors.forename: Marte
authors.initials: M
authors.lastname: Thuen
authors.forename: Einar
authors.initials: E
authors.lastname: Vik-Mo
authors.forename: Mrinal
authors.initials: M
authors.lastname: Joel
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Perreault
authors.forename: Iver A
authors.initials: IA
authors.lastname: Langmoen
authors.forename: Olav
authors.initials: O
authors.lastname: Haraldseth
authors.forename: Joel C
authors.initials: JC
authors.lastname: Glover
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D058948:Cell Tracking; D002642:Chick Embryo; D002645:Chickens; D005290:Ferric Compounds / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D016867:Immunocompromised Host; D008279:Magnetic Resonance Imaging; D059630:Mesenchymal Stem Cells / Q000737:chemistry / Q000166:cytology; D051379:Mice; D018613:Microscopy, Confocal; D008938:Mitosis / Q000187:drug effects; D058953:Neural Stem Cells / Q000737:chemistry / Q000166:cytology; D010316:Particle Size; D013234:Stem Cells / Q000737:chemistry / Q000166:cytology*
chemical_list: D005290:Ferric Compounds; C000499:ferric oxide