Tracking of systemically administered mononuclear cells in the ischemic brain by high-field magnetic resonance imaging.
This study was designed to track systemically administered mononuclear cells (MNCs) in the ischemic mouse brain using 7 T magnetic resonance imaging (MRI). Splenectomized wild-type mice were subjected to brain ischemia by 30 or 60 min filamentous occlusion of the middle cerebral artery (MCAo) and reperfusion. Spleen-derived MNCs were labeled with very small superparamagnetic iron-oxide particles (VSOP) and transfused into recipient mice 30 min, 8 h, or 24 h after MCAo via the tail vein. High-resolution MRI sequences were designed to monitor the dynamics of brain ischemia and to observe the migration and engraftment of transfused cells into the ischemic brain. T2*-weighted (gradient-echo) hypointense signal changes became apparent at 24-48 h after transfusion, were typically associated with the ischemic lesion border, and could be followed up to 5 weeks after the insult. Such presumed MNC-associated signal changes in MRI were confirmed by histochemical detection of iron (Prussian blue staining) and detection of constitutively expressed green fluorescent protein (GFP) in a subset of animals transfused with MNCs derived from GFP transgenic mice. Taken together, our results demonstrate that brain engraftment of systemically administered mononuclear cells can be visualized non-invasively over time and space using high-resolution MRI.
Stroh
Albrecht
A
Department of Radiology, Charité-Universitaetsmedizin Berlin, Schumannstrasse 20-21, 10117 Berlin, Germany. astroh@stanford.edu
Zimmer
Claus
C
Werner
Nikos
N
Gertz
Karen
K
Weir
Kathrine
K
Kronenberg
Golo
G
Steinbrink
Jens
J
Mueller
Susanne
S
Sieland
Katharina
K
Dirnagl
Ulrich
U
Nickenig
Georg
G
Endres
Matthias
M
D000818:Animals; D001803:Blood Transfusion; D001921:Brain / Q000473:pathology*; D002545:Brain Ischemia / Q000473:pathology*; D005290:Ferric Compounds; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000502:physiology*; D015427:Reperfusion Injury / Q000473:pathology; D013154:Spleen / Q000166:cytology; D013156:Splenectomy
D005290:Ferric Compounds; C000499:ferric oxide