title: Magnetic Resonance Imaging Tracking of Graft Survival in the Infarcted Heart: Iron Oxide Particles Versus Ferritin Overexpression Approach.
abstract: The main objective of cell therapy is the regeneration of damaged tissues. To distinguish graft from host tissue by magnetic resonance imaging (MRI), a paramagnetic label must be introduced to cells prior to transplantation. The paramagnetic label can be either exogenous iron oxide nanoparticles or a genetic overexpression of ferritin, an endogenous iron storage protein. The purpose of this work was to compare the efficacy of these 2 methods for MRI evaluation of engrafted cell survival in the infarcted mouse heart. Mouse skeletal myoblasts were labeled either by cocultivation with iron oxide particles or by engineering them to overexpress ferritin. Along with live cell transplantation, 2 other groups of mice were injected with dead-labeled cells. Both particle-labeled and ferritin-tagged grafts were detected as areas of MRI signal hypointensity in the left ventricle of the mouse heart using T2*-weighted sequences, although the signal attenuation decreased with ferritin tagging. Importantly, live cells could not be distinguished from dead cells when labeled with iron oxide particles, whereas the ferritin tagging was detected only in live grafts, thereby allowing identification of viable grafts using MRI. Thus, iron oxide particles can provide information about initial cell injection success but cannot assess graft viability. On the other hand, genetically based cell tagging, such as ferritin overexpression, despite having lower signal intensity in comparison with iron oxide particles, is able to identify live transplanted cells.
authors.affiliation: Department of Radiology, University of Washington, Seattle, WA, USA Center for Cardiovascular Biology, University of Washington, Seattle, WA, USA Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, USA nav@uw.edu.
authors.forename: Anna V
authors.initials: AV
authors.lastname: Naumova
authors.affiliation: Department of Radiology, University of Washington, Seattle, WA, USA Center for Cardiovascular Biology, University of Washington, Seattle, WA, USA.
authors.forename: Niranjan
authors.initials: N
authors.lastname: Balu
authors.affiliation: Department of Radiology, University of Washington, Seattle, WA, USA Center for Cardiovascular Biology, University of Washington, Seattle, WA, USA.
authors.forename: Vasily L
authors.initials: VL
authors.lastname: Yarnykh
authors.affiliation: Center for Cardiovascular Biology, University of Washington, Seattle, WA, USA Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, USA Department of Pathology, University of Washington, Seattle, WA, USA.
authors.forename: Hans
authors.initials: H
authors.lastname: Reinecke
authors.affiliation: Center for Cardiovascular Biology, University of Washington, Seattle, WA, USA Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, USA Department of Pathology, University of Washington, Seattle, WA, USA Department of Bioengineering, University of Washington, Seattle, WA, USA Department of Medicine/Cardiology, University of Washington, Seattle, WA, USA.
authors.forename: Charles E
authors.initials: CE
authors.lastname: Murry
authors.affiliation: Department of Radiology, University of Washington, Seattle, WA, USA Center for Cardiovascular Biology, University of Washington, Seattle, WA, USA Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, USA Department of Bioengineering, University of Washington, Seattle, WA, USA.
authors.forename: Chun
authors.initials: C
authors.lastname: Yuan
keywords: acute myocardial infarction; cell transplantation; ferritin; gene reporter; iron oxide nanoparticles; magnetic resonance imaging