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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Magnetic resonance imaging overestimates ferumoxide-labeled stem cell survival after transplantation in the heart
Circulation, Volume 117, No. 12, Year 2008
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Description
BACKGROUND - Stem cell labeling with iron oxide (ferumoxide) particles allows labeled cells to be detected by magnetic resonance imaging (MRI) and is commonly used to track stem cell engraftment. However, the validity of MRI for distinguishing surviving ferumoxide-labeled cells from other sources of MRI signal, for example, macrophages containing ferumoxides released from nonsurviving cells, has not been thoroughly investigated. We sought to determine the relationship between the persistence of iron-dependent MRI signals and cell survival 3 weeks after injection of syngeneic or xenogeneic ferumoxides-labeled stem cells (cardiac-derived stem cells) in rats. METHODS AND RESULTS - We studied nonimmunoprivileged human and rat cardiac-derived stem cells and human mesenchymal stem cells doubly labeled with ferumoxides and β-galactosidase and injected intramyocardially into immunocompetent Wistar-Kyoto rats. Animals were imaged at 2 days and 3 weeks after stem cell injection in a clinical 3-T MRI scanner. At 2 days, injection sites of xenogeneic and syngeneic cells (cardiac-derived stem cells and mesenchymal stem cells) were identified by MRI as large intramyocardial signal voids that persisted at 3 weeks (50% to 90% of initial signal). Histology (at 3 weeks) revealed the presence of iron-containing macrophages at the injection site, identified by CD68 staining, but very few or no β-galactosidase-positive stem cells in the animals transplanted with syngeneic or xenogeneic cells, respectively. CONCLUSIONS - The persistence of significant iron-dependent MRI signal derived from ferumoxide-containing macrophages despite few or no viable stem cells 3 weeks after transplantation indicates that MRI of ferumoxide-labeled cells does not reliably report long-term stem cell engraftment in the heart. © 2008 American Heart Association, Inc.
Authors & Co-Authors
Terrovitis, John
United States, Baltimore
Johns Hopkins University
Stuber, Matthias
United States, Baltimore
Division of mr Research
Youssef, Amr
United States, Baltimore
Johns Hopkins University
Egypt, Cairo
Ain Shams University
Preece, Steve
United States, Baltimore
Johns Hopkins University
Leppo, Michelle
United States, Baltimore
Johns Hopkins University
Kizana, Eddy
United States, Baltimore
Johns Hopkins University
Schär, Michael
United States, Baltimore
Division of mr Research
Netherlands, Eindhoven
Philips Healthcare Nederland
Gerstenblith, Gary
United States, Baltimore
Johns Hopkins University
Weiss, Robert G.
United States, Baltimore
Johns Hopkins University
Marbán, Eduardo
United States, Baltimore
Johns Hopkins University
United States, Los Angeles
Cedars-sinai Medical Center
Abraham, M. Roselle
United States, Baltimore
Johns Hopkins University
Statistics
Citations: 252
Authors: 11
Affiliations: 5
Identifiers
Doi:
10.1161/CIRCULATIONAHA.107.732073
ISSN:
00097322
Research Areas
Cancer
Noncommunicable Diseases