Inhibited atherosclerotic plaque formation by local administration of magnetically labeled endothelial progenitor cells (EPCs) in a rabbit model.

PURPOSE: To investigate whether atherosclerosis can be prevented by magnetically labeled endothelial progenitor cells (EPCs) in rabbits.
MATERIALS AND METHODS: EPCs derived from rabbit periphery blood were labeled with a superparamagnetic iron oxide (SPIO) agent Fe(2)O(3)-poly-L-lysine (Fe(2)O(3)-PLL). Rabbit atherosclerosis was induced by high-cholesterol-diet following balloon injury via catheterization of right common carotid artery (RCCA). Fe(2)O(3)-PLL labeled EPCs (2 x 10(6)) and media were allowed to interact with the RCCA for 25 min in EPC-treated rabbits (n=14) and control rabbits (n=7) animals respectively. MRI was performed with a 1.5T-magnet to measure RCCA signal intensity (SI) and caliber at week 1, 2, 3, 6, 12, and 15 with animals euthanized in groups for histopathology.
RESULTS: In EPC-treated rabbits, T(2)(*)-weighted MRI showed SI loss in RCCA at week 1 and 2 followed by normalization after week 3. MRI outcomes corresponded well to findings of Prussian blue staining. MRI at week 6, 12 and 15 showed little stenosis of RCCA in EPC-treated rabbits, but moderate to severe stenoses in control rabbits. Histology at week 15 revealed significantly thinner RCCA wall (277.62 microm vs. 382.95 microm, P=0.026), greater internal diameter (913.33 microm vs. 789.64 microm, P=0.037) and smaller plaque (398.60mm(2) vs. 597.70 mm(2), P=0.047) in EPC-treated rabbits relative to control rabbits.
CONCLUSION: Atherosclerosis at RCCA was inhibited by SPIO-labeled EPCs, which was depicted with a clinical MRI scanner over 2 weeks after cell administration, suggesting that EPCs may play a role in restoration of endothelial injury and prevention of atherosclerosis.