on September 2, 2003
Published online before print September 2, 2003, doi: 10.1161/01.CIR.0000089084.48655.49
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Submitted on January 28, 2003
From the Division of Cardiovascular Diseases and Internal Medicine (R.G., T.E.P., T.A.W., L.S.K., C.S.M., A.L., R.D.S.), the Molecular Medicine Program (R.G., D.J., T.E.P., T.A.W., L.S.K., C.S.M., R.G.V., R.D.S.), and the Department of Biochemistry and Molecular Biology (R.D.S.), Mayo Clinic, Rochester, Minn. * To whom correspondence should be addressed. E-mail: simari.robert{at}mayo.edu.
Background--Bone marrow-derived cells have been shown to contribute to endothelial replacement after vascular injury. In vitro culture of peripheral blood mononuclear cells produces cells with phenotypic characteristics of endothelium. To test the hypothesis that delivery of autologous culture-modified mononuclear cells (CMMCs) to injured arteries could attenuate the vascular response to injury, a rabbit model was studied. Methods and Results--Rabbit peripheral blood mononuclear cells were cultured in endothelial growth media for 7 to 12 days, yielding highly proliferative cells with distinct endothelial phenotype (expressing CD31 and endothelial nitric oxide synthase and capable of acetylated LDL uptake). A rabbit model of balloon carotid injury was used to evaluate the effect of day 7 CMMC delivery on vascular responses. Animals underwent balloon injury and immediate delivery of autologous CMMCs or buffered saline by 20 minutes of local dwelling. Fluorescence-labeled CMMCs were detected in all vessel layers 4 weeks after delivery. Colonies of cells that localized to the lumen and stained for endothelial markers were also identified. Local CMMC administration at the time of balloon injury accelerated reendothelialization at 4 weeks compared with saline (P<0.05). Moreover, CMMC delivery markedly improved endothelium-dependent vasoreactivity at 4 weeks compared with saline (P<0.005). Finally, CMMC treatment reduced neointimal formation by 55% at 4 weeks (P<0.05). Conclusions--These data demonstrate that delivery of CMMCs to balloon-injured arteries is associated with accelerated reendothelialization, enhanced endothelium-dependent vasoreactivity, and reduced neointimal formation. Thus, delivery of autologous CMMCs represents a novel vasculoprotective approach to attenuate the response to acute vascular injury.
Revised on May 28, 2003
Accepted on May 28, 2003
Autologous Culture-Modified Mononuclear Cells Confer Vascular Protection After Arterial Injury
Rajiv Gulati MD, MRCP,
Key words: atherosclerosis • endothelium • cells • restenosis
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