Abstract 12993: Administration of Echogenic Immunoliposome-Targeted CD146 + Mesenchymal Stem Cells Reduces Hypercholesterolemia and Atherosclerosis

Abstract

Introduction and Hypothesis: Mesenchymal stem cells (MSC) have been used to treat atherosclerosis and diabetes in animal studies and clinical trials. We developed a nanotechnology in which MSC can be targeted with anti-CD146/ICAM bifunctional (BF) echogenic immunoliposomes (ELIP) for treatment of atherosclerosis. Here, we tested the hypothesis that BF-ELIP targeted MSC therapy is biologically safe and effective for preventing hypercholesterolemia and atheroma. Methods and Results: BF-ELIP with antibodies to the mesenchymal marker CD146 and the adhesion protein ICAM-1 were mixed with CD146 + MSC grown from adipose tissue of green fluorescence protein (GFP)-transgenic mice. The BF-ELIP/MSC mixtures or controls, such as non-immune ELIP (NE)/MSC mixtures, NE and MSC alone, were intravenously administered to C57BL/6J wild type (WT) and apolipoprotein-E deficient (ApoE -/- ) mice, which were age-/sex-matched. In a nearly 4 months followup, all the mice survived the ELIP/MSC injection without major adverse effects observed. No major difference in blood pressure was found between ELIP/MSC-treated and non-MSC controls. Total cholesterol and glucose were examined in blood samples collected from the animals. ApoE -/- mice developed significantly higher cholesterol (p<0.05) but lower glucose (p<0.05) levels than WT mice. The BF-ELIP targeted MSC injection reduced levels of total cholesterol and, to a lesser extent, glucose (p<0.05). Non-invasive ultrasound confirmed enhancement of ELIP echogenicity and imaging of atheroma. Fluorescence microscopy illustrated GFP expression in the MSC mixtures and the arterial wall with atheroma. H&E and Oil-Red O staining showed reduced plaque formation and lipid loading in the arterial wall of ApoE -/- but not WT mice with the MSC delivery. Conclusions: Administration of BF-ELIP targeted MSCs appears to be a safe, effective procedure, which may mitigate hypercholesterolemia and atherogenesis.