Magnetic resonance imaging overestimates ferumoxide-labeled stem cell survival after transplantation in the heart.

Details

Serval ID
serval:BIB_E39487AD6D13
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Magnetic resonance imaging overestimates ferumoxide-labeled stem cell survival after transplantation in the heart.
Journal
Circulation
Author(s)
Terrovitis J., Stuber M., Youssef A., Preece S., Leppo M., Kizana E., Schär M., Gerstenblith G., Weiss R.G., Marbán E., Abraham M.R.
ISSN
1524-4539[electronic], 0009-7322[linking]
Publication state
Published
Issued date
2008
Volume
117
Number
12
Pages
1555-1562
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
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 beta-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 beta-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.
Keywords
Animals, Cell Survival, Ferrosoferric Oxide, Humans, Iron/diagnostic use, Macrophages, Magnetic Resonance Imaging/methods, Magnetic Resonance Imaging/standards, Mesenchymal Stem Cell Transplantation, Mesenchymal Stem Cells/cytology, Myocardium/cytology, Oxides/diagnostic use, Rats, Rats, Inbred WKY, Transplantation, Heterologous, Transplantation, Homologous
Pubmed
Web of science
Open Access
Yes
Create date
02/03/2010 17:04
Last modification date
20/08/2019 17:07
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