Submitted on June 9, 2006
Revised on December 21, 2006
Accepted on December 23, 2006
Impaired therapeutic vasculogenesis by transplantation of OxLDL-treated endothelial progenitor cells
Bin Zhou, Feng Xia Ma, Peng Xia Liu, Zhi hong Fang, Sili Wang, Zhi Han, Man-Chiu Poon, and Zhong Chao Han
hematology, Tianjin, Tianjin 300020
Corresponding Author: bzhoupumc{at}gmail.com
Previous in vitro study has revealed that OxLDL has negative effect 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 3×105 EPCs. By laser Doppler perfusion image and ischemia damage score, we found that blood perfusion and ischemia damage was less well recovered in OxLDL-treated EPCs transplantation group than controls. Histological examination showed less transplanted EPCs and lower capillary density in ischemic tissue. Local delivery of SDF-1a restored this defect and improved blood perfusion by recruiting OxLDL-treated EPCs to 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. Therapeutic strategy based on SDF-1a administration ameliorated such defects and improved post-ischemic neovascularization.
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