Abstract 15904: Echogenic Immunoliposome-targeted Mesenchymal Stem Cells for Imaging and Treatment of Atheroma

Abstract

Background: Vascular stem cell dead impairs the regenerating capacity of the arterial wall with atherosclerosis. A patented technology has been developed to employ biofunctional echogenic immunoliposomes (BF-ELIP) for enhancing entry of stem cells to atherosclerotic lesions. Objective: Determine whethere ultrasound-enhanced delivery of BF-ELIP-targeted stem cells visualize and treat atheroma simultaneously. Methods and Results: BF-ELIP were prepared by conjugating thiolated antibodies specific for the mesenchymal marker CD146 and murine ICAM-1 to phosphatidyl-ethanolamine liposomes through a thioether linkage. CD146 + bone marrow-derived mesenchymal cells (BM-MSC) were prepared from green fluorescence protein (GFP)-transgenic mice. By fluorescence microscopy, BF-ELIP targeted CD146 + cells were clearly visualized being adherent on cultured human endothelial cells that expressed ICAM-1 induced by tumor necrosis factor alpha (TNF-α) (Fig. 1a). BM-MSC/BF-ELIP mixtures were intravenously injected into ApoE-/- mice (n=9). Ultrasound illustrated intense echo signals of BF-ELIP in the aortic arch 15 min after injection of the BM-MSC/BF-ELIP preparation into ApoE-knockout mice (Fig. 1b). Histopathology of the aorta analyzed by H&E and Oil-Red O staining of aortic sections showed that the BF-ELIP targeted MSC delivery reduced plaque sizes, inflammation and lipid loading. Neither normal wild type C57BL/6J nor ApoE-knockout mice without injection showed the intensified echo signals and histological changes in their aortic arch regions. Conclusions: BF-ELIP enhancement of vascular stem cell adherence to inflammatory endothelium facilitates vulnerable plaque detection and targeted stem cell therapy for atheroma. This proof of concept study illustrates on the development of ultrasound-enhanced, BF-ELIP-mediated stem cell delivery and therapeutic approach to stabilize atheroma.