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Superparamagnetic Iron Oxide Labeling and Transplantation of Adipose-Derived Stem Cells in Middle Cerebral Artery Occlusion-Injured Mice

¹ Department of Surgery, Duke University Medical Center, Box 3815, Durham, NC 27710.
² Department of Biomedical Engineering, Duke University Medical Center, Durham, NC.
³ Department of Anesthesiology, Duke University Medical Center, Durham, NC.
⁴ Department of Radiology, Duke University Medical Center, Durham, NC.

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.

MATERIALS AND 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.

CONCLUSION. 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.

Keywords: brain • ischemia • MRI • stem cells • transplantation

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