Superparamagnetic iron oxide labeling and transplantation of adipose-derived stem cells in middle cerebral artery occlusion-injured mice.
OBJECTIVE
Adipose-derived stem cells are an alternative stem cell source for CNS therapies. The goals of the current study were to label adipose-derived stem cells with superparamagnetic iron oxide (SPIO) particles, to use MRI to guide the transplantation of adipose-derived stem cells in middle cerebral artery occlusion (MCAO)-injured mice, and to localize donor adipose-derived stem cells in the injured brain using MRI. We hypothesized that we would successfully label adipose-derived stem cells and image them with MRI.


METHODS
Adipose-derived stem cells harvested from mice inbred for green fluorescent protein were labeled with SPIO ferumoxide particles through the use of poly-L-lysine. Adipose-derived stem cell viability, iron staining, and proliferation were measured after SPIO labeling, and the sensitivity of MRI in the detection of SPIO-labeled adipose-derived stem cells was assessed ex vivo. Adult mice (n = 12) were subjected to unilateral MCAO. Two weeks later, in vivo 7-T MRI was performed to guide stereotactic transplantation of SPIO-labeled adipose-derived stem cells into brain tissue adjacent to the infarct. After 24 hours, the mice were sacrificed for high-resolution ex vivo 7-T or 9.4-T MRI and histologic study.


RESULTS
Adipose-derived stem cells were efficiently labeled with SPIO particles without loss of cell viability or proliferation. Using MRI, we guided precise transplantation of adipose-derived stem cells. MR images of mice given injections of SPIO-labeled adipose-derived stem cells had hypointense regions that correlated with the histologic findings in donor cells.


CONCLUSIONS
MRI proved useful in transplantation of adipose-derived stem cells in vivo. This imaging technique may be useful for studies of CNS stem cell therapies.
Rice
Henry E
HE
Department of Surgery, Duke University Medical Center, Box 3815, Durham, NC 27710, USA.
Hsu
Edward W
EW
Sheng
Huaxin
H
Evenson
Debra A
DA
Freemerman
Alex J
AJ
Safford
Kristine M
KM
Provenzale
James M
JM
Warner
David S
DS
Johnson
G Allan
GA
D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D002545:Brain Ischemia / Q000175:diagnosis* / Q000209:etiology / Q000601:surgery*; D003287:Contrast Media; D003911:Dextrans; D052203:Ferrosoferric Oxide; D020244:Infarction, Middle Cerebral Artery / Q000150:complications*; D007501:Iron; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles; D051379:Mice; D008810:Mice, Inbred C57BL; D010087:Oxides; D033581:Stem Cell Transplantation / Q000379:methods*
D003287:Contrast Media; D003911:Dextrans; D058185:Magnetite Nanoparticles; D010087:Oxides; C097921:ferumoxtran-10; D007501:Iron; D052203:Ferrosoferric Oxide