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


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.
Terrovitis
John
J
Johns Hopkins University, Division of Cardiology, Department of Medicine, Rutland Ave, Baltimore, MD 21205, USA.
Stuber
Matthias
M
Youssef
Amr
A
Preece
Steve
S
Leppo
Michelle
M
Kizana
Eddy
E
Schär
Michael
M
Gerstenblith
Gary
G
Weiss
Robert G
RG
Marbán
Eduardo
E
Abraham
M Roselle
MR
D000818:Animals; D002470:Cell Survival; D003911:Dextrans; D052203:Ferrosoferric Oxide; D006801:Humans; D007501:Iron; D008264:Macrophages; D008279:Magnetic Resonance Imaging / Q000379:methods* / Q000592:standards; D058185:Magnetite Nanoparticles; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D009206:Myocardium / Q000166:cytology*; D010087:Oxides; D051381:Rats; D011921:Rats, Inbred WKY; D014183:Transplantation, Heterologous; D014184:Transplantation, Homologous
D003911:Dextrans; D058185:Magnetite Nanoparticles; D010087:Oxides; D007501:Iron; C065507:ferumoxides; D052203:Ferrosoferric Oxide