Non-invasive tracking of human haemopoietic CD34(+) stem cells in vivo in immunodeficient mice by using magnetic resonance imaging.
OBJECTIVE
To assess migration of CD34(+) human stem cells to the bone marrow of athymic mice by using magnetic resonance (MR) imaging and Resovist, a contrast agent containing superparamagnetic iron oxide (SPIO) particles.


METHODS
All animal and human procedures were approved by our institution's ethics committee, and women had given consent to donate umbilical cord blood (UCB). Balb/c-AnN Foxn1(nu)/Crl mice received intravenous injection of 1 x 10(6) (n=3), 5 x 10(6) (n=3) or 1 x 10(7) (n=3) human Resovist-labelled CD34(+) cells; control mice received Resovist (n=3). MR imaging was performed before, 2 and 24 h after transplantation. Signal intensities of liver, muscle and bone marrow were measured and analysed by ANOVA and post hoc Student's t tests. MR imaging data were verified by histological and immunological detection of both human cell surface markers and carboxydextrancoating of the contrast agent.


RESULTS
CD34(+) cells were efficiently labelled by Resovist without impairment of functionality. Twenty-four hours after administration of labelled cells, MR imaging revealed a significant signal decline in the bone marrow, and histological and immunological analyses confirmed the presence of transplanted human CD34(+) cells.


CONCLUSIONS
Intravenously administered Resovist-labelled CD34(+) cells home to bone marrow of mice. Homing can be tracked in vivo by using clinical 1.5-T MR imaging technology.
Niemeyer
Markus
M
Department of Gynaecology, Klinikum rechts der Isar, Technische Universität München, Ismaninger Str. 22, 81675 Munich, Germany. markus.niemeyer@gmx.net
Oostendorp
Robert A J
RA
Kremer
Markus
M
Hippauf
Sandra
S
Jacobs
Volker R
VR
Baurecht
Hansjörg
H
Ludwig
Georg
G
Piontek
Guido
G
Bekker-Ruz
Viktoria
V
Timmer
Sebastian
S
Rummeny
Ernst J
EJ
Kiechle
Marion
M
Beer
Ambros J
AJ
D000818:Animals; D058948:Cell Tracking / Q000379:methods*; D002478:Cells, Cultured; D017074:Common Variable Immunodeficiency / Q000276:immunology* / Q000473:pathology* / Q000601:surgery; D003287:Contrast Media; D003911:Dextrans; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D016867:Immunocompromised Host / Q000276:immunology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D013194:Staining and Labeling / Q000379:methods
D003287:Contrast Media; D003911:Dextrans; D058185:Magnetite Nanoparticles; C065507:ferumoxides
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