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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:2636.)
© 2005 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Transfer of Endothelial Progenitor and Bone Marrow Cells Influences Atherosclerotic Plaque Size and Composition in Apolipoprotein E Knockout Mice

Jacob George; Arnon Afek; Anastasia Abashidze; Haim Shmilovich; Varda Deutsch; Juri Kopolovich; Hylton Miller; Gad Keren

From the Department of Cardiology (J.G., A. Abashidze, H.S., H.M., G.K.), Tel Aviv Sourasky Medical Center Affiliated to the Sackler Faculty of Medicine, Tel Aviv University, Israel; Institute of Pathology (A. Afek, J.K.), Sheba Medical Center, Tel Aviv University, Israel; and the Institute of Hematology (V.D.), Tel Aviv Medical Center, Israel.

Reprint requests to Jacob George, MD, The Department of Cardiology, Tel Aviv Sourasky Medical Center, 6 Weizmann St, Tel Aviv, Israel. E-mail jacobg{at}post.tau.ac.il

Objectives— Recent clinical trials use cell therapy with bone marrow (BM) cells or endothelial progenitor cells (EPCs) for ischemic syndromes. We explored the effect of BM cell– or spleen cell–derived EPC transfer on plaque size and stability markers in the apolipoprotein E knockout (apoE KO) mouse model.

Methods and Results— ApoE KO mice aged 10 weeks served as recipients. Labeled BM cells and spleen cell–derived EPCs from age-matched apoE KO mice were injected intravenously to 2 groups of recipient mice each. Additional mice served as controls receiving saline. Both protocols were repeated 3 times at 2 weekly intervals. On killing, plaque size and character were studied, lipid profile analyzed, and serum and aortic cytokines assayed. Spleen cell–derived cells contained a significantly larger number of endothelial cell precursors. Labeled EPCs and BM cells were found abundantly in the spleens, yet also in the lesions of the recipient mice. Aortic sinus lesion size was significantly increased in mice receiving BM cells (n=10) in the EPC-treated group (n=10) compared with controls (n=10; a 54% and a 34% increase in aortic sinus plaque area, respectively). Mice receiving EPCs exhibited plaques with larger lipid cores and thinner fibrous caps and a higher number of infiltrating CD3 cells. RT-PCR analysis of aortas revealed reduced expression of mRNA for interleukin-10 (IL-10) in both cell transfer groups. Higher serum concentrations of IL-6 and monocyte chemoattractant protein-1 were found in sera from BM recipients, whereas lower IL-10 levels were found in mice transfused with spleen-derived EPCs.

Conclusions— Transfer of BM cells and EPCs may result in an increase in atherosclerotic lesion size, whereas EPC transfer could also potentially influence plaque stability.

Transfer of EPCs and BM cells significantly increased plaque size in apoE KO mice, whereas only the former treatment was associated with destabilization of the lesions. BM cell and EPC transfer reduced aortic expression of IL-10. Thus, cell therapy with BM cells should be used with caution in clinical trials.

Key Words: stem cells • cell therapy • atherosclerosis • inflammation • endothelial progenitor cells

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