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Originally published In Press as doi:10.1194/jlr.M600251-JLR200 on December 24, 2006

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Journal of Lipid Research, Vol. 48, 518-527, March 2007
Copyright © 2007 by American Society for Biochemistry and Molecular Biology

Impaired therapeutic vasculogenesis by transplantation of OxLDL-treated endothelial progenitor cells

Bin Zhou*, Feng Xia Ma*, Peng Xia Liu*, Zhi Hong Fang*, Si Li Wang*, Zhi Bo Han*, Man-Chiu Poon*,{dagger} and Zhong Chao Han1,*

* State Key Laboratory of Experimental Hematology, National Research Center for Stem Cell Engineering and Technology, Institute of Hematology, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
{dagger} Department of Medicine, University of Calgary, Calgary, Alberta, Canada

Published, JLR Papers in Press, December 24, 2006.

1 To whom correspondence should be addressed. e-mail: tihzchan{at}public.tpt.tj.cn

Previous in vitro studies have revealed that oxidized low density lipoprotein (OxLDL) has negative effects on the proliferation and activity of endothelial progenitor cells (EPCs). Here, we evaluated the effect of OxLDL on the therapeutic potential of EPCs in ischemia-induced neovascularization. EPCs derived from mobilized human peripheral blood mononuclear cells were cultured without or with OxLDL before transplantation. Hindlimb ischemia models were surgically induced in athymic nude mice, which then received an intracardiac injection of 3 x 105 EPCs. By laser Doppler perfusion image and ischemia damage score, we found that blood perfusion and ischemia damage were less well recovered in the OxLDL-treated EPC transplantation group than in controls. Histological examination showed fewer transplanted EPCs and lower capillary density in ischemic tissue. Local delivery of Stromal cell-derived factor (SDF-1) restored this defect and improved blood perfusion by recruiting OxLDL-treated EPCs to the ischemic area and increasing host capillary density. These results provide for the first time direct evidence that OxLDL impaired the therapeutic potential of EPCs in ischemia-induced neovascularization through an inhibitory effect on the migration, adhesion, and incorporation of EPCs into vasculature and/or entrapment in the perivascular region in vivo. A therapeutic strategy based on SDF-1 administration ameliorated such defects and improved postischemic neovascularization.

Supplementary key words oxidized low density lipoprotein • ischemia • stromal cell-derived factor


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