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1 Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic College of Medicine, Rochester, MN, USA; Molecular Medicine Program, Mayo Clinic College of Medicine, Rochester, MN, USA
2 Molecular Medicine Program, Mayo Clinic College of Medicine, Rochester, MN, USA
3 Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic College of Medicine, Rochester, MN, USA
4 Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic College of Medicine, Rochester, MN, USA; Molecular Medicine Program, Mayo Clinic College of Medicine, Rochester, MN, USA; Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN, USA
* To whom correspondence should be addressed. E-mail: simari.robert{at}mayo.edu.
Delivery of a heterogeneous population of cells with endothelial phenotype derived from peripheral blood has been shown to improve vascular responses after balloon arterial injury in an endothelial-dependent manner. Refinement of culture-techniques have enabled the generation of outgrowth endothelial cells (OECs), a homogeneous population of distinctly endothelial cells expanded from circulating precursors. The present study tested the hypothesis that OEC delivery would confer vascular protection after balloon arterial injury in a rabbit model. Rabbit PBMCs were cultured in endothelial growth media for 4-5 weeks yielding proliferative OECs with distinct endothelial phenotype (morphology, incorporation of acetylated LDL, expression of endothelial nitric oxide synthase and caveolin-1 but not CD14). Animals underwent balloon carotid injury immediately followed by local delivery of autologous OECs for 20 minutes. Fluorescentlabeled OECs were detected in all layers at 4 weeks, immunostaining revealing maintenance of endothelial phenotype (vWF+, RAM-11-) by both luminal and nonluminal cells. To evaluate functional effects, additional animals received autologous OECs, saline, or freshly-harvested PBMCs as non-cultured cell controls by local dwell after balloon injury. Local OEC delivery improved endothelial-dependent vasoreactivity (p<0.05 vs saline and PBMC) and similarly reduced neointimal formation (p<0.05 vs. saline and PBMC). These data suggest that OECs can be detected in injured arterial segments at 4 weeks. Moreover, delivery of OECs confers greater vascular protection than PBMCs or saline controls and may thus offer a novel, autologous strategy to limit the response to mechanical injury.
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