Abstract 19643: Transplantation of Bone Marrow Stem Cells Complexed With Immunoliposomes Targeted to Cd34 and Icam-1 Reduces Atherosclerosis in Apolipoprotein-e Null Mice
Background: Transplantation of bone marrow stem cells (BMSC) offers a novel therapy for myocardial infarction caused by atherosclerosis. The mechanism behind the therapeutic effect of BMSC is not well understood. This study was to test the impact of selective delivery of BMSC to atherosclerotic arteries using targeted echogenic immunoliposomes (ELIP).
Methods and Results: BMSC containing CD34+ vascular stem cells (VSC) were complexed with ELIP conjugated to anti-CD34/ICAM-1 antibodies or IgG (controls). The BMSP labeled with ELIP (2x106/25g body weight) were intravenously transfused into wild type (n=12) and apolipoprotein-E (apoE)-null (n=12) C57BL/6J mice. Little or no plaque signals were visualized by ultrasound in wild type mice. In contrast, apoE-null mice receiving ELIP displayed acoustic enhancement in the aorta with atheroma, but not in other areas, providing evidence that stem cells targeted with ELIP were adhering specifically to atheroma. The impact of ELIP-targeted delivery of stem cells on the development of atheroma was determined 45 days after transplantation of the bone marrow cells with ELIP or IgG controls. Compared to the controls, apoE-null mice receiving ELIP-stem cells showed significant reductions in total cholesterol (459 mg/dL control vs. 310 mg/dL in BF-ELIP, p<0.05), LDL (394 mg/dL vs. 246 mg/dL, p<0.05), as well as in Oil-Red O staining. Histopathological analysis demonstrated less plaque with high stem cell numbers (Figure). The plaque cap was thicker and core contained fewer lipids.
Conclusion: Transplantation of stem cells targeted with ELIP can reduce hypercholesterolemia and inhibit atherogenesis. Furthermore, the targeted stem cell delivery stabilizes the plaque tissue with increased vascular cells and a thicker cap. Figure. H&E staining of aortic sections of apoE-null mice with (upper) or without (lower) ELIP-BMSC. Arrow indicates a thin-cap, rupture-prone plaque.
- © 2010 by American Heart Association, Inc.