Delivery of Stem Cells to Porcine Arterial Wall with Echogenic Liposomes Conjugated to Antibodies against CD34 and Intercellular Adhesion Molecule-1

Abstract

In atherosclerosis, the loss of vascular stem cells via apoptosis impairs the capacity of the vascular wall to repair or regenerate the tissue damaged by atherogenic factors. Recruitment of exogenous stem cells to the plaque tissue may repopulate vascular cells and help repair the arterial tissue. Ultrasound-enhanced liposomal targeting may provide a feasible method for stem cell delivery into atheroma. Bifunctional echogenic immunoliposomes (BF-ELIP) were generated by covalently coupling two antibodies to liposomes; the first one specific for CD34 antigens on the surface of stem cells and the second directed against the intercellular adhesion molecule-1 (ICAM-1) antigens on the inflammatory endothelium covering atheroma. CD34+ stem cells from adult bone marrow were incubated on the ICAM-1-expressing endothelium of the aorta of swine fed high cholesterol diets, which was preloaded with BF-ELIP. Significantly increased stem cell adherence and penetration were detected, in particular in the aortic segments treated with 1 MHz low-amplitude continuous wave ultrasound. Fluorescence and scanning electron microscopy confirmed the presence of BF-ELIP-bound CD34+ cells in the intimal compartment of the atheromatous arterial wall. Ultrasound treatment increased the number of endothelial cell progenitors migrating into the intima. Thus, under ultrasound enhancement, BF-ELIP bound CD34+ stem cells selectively bind to the ICAM-1 expressing endothelium of atherosclerotic lesions.

Liposomes in tissue engineering and regenerative medicine

“…Active release relies on developing mechanisms to increase the permeability or to destabilize the liposome bilayer once it reaches the target site. A variety of stimuli such as pH [46,98], temperature [39,99], ultrasonic waves [100], magnetic fields [101,102] and light [103,104] are currently being investigated to improve the target release of bioactive agent. Although the concept of triggered release is very promising, more studies have to be performed to prove its application in humans [17].…”

Encapsulated microbubbles and echogenic liposomes for contrast ultrasound imaging and targeted drug delivery

“…Anti-intercellular adhesion molecule-1 (ICAM-1) [224–227], anti-vascular cell adhesion molecule (VCAM-1), anti-fibrin, anti-fibrinogen and anti-tissue factor conjugated with ELIPs [68, 228] have also been developed to achieve both in vitro and in vivo targeting. ELIPs can be loaded with both hydrophilic and lipophilic molecules [70].…”

Relationship between cavitation and loss of echogenicity from ultrasound contrast agents

“…ELIP are lipid bilayer vesicles, ranging from 40 nm to 6 μm in diameter (Kopechek et al 2011), each encapsulating an aqueous core and gas pocket (Huang 2008, Kopechek et al 2011). ELIP can be loaded with several cardiovascular therapeutic agents (Britton et al 2010, Buchanan et al 2010, Herbst et al 2010, Tiukinhoy-Laing et al 2007, Huang et al 2007, Huang et al 2009) and targeted to specific molecular receptors in diseased vasculature (Hamilton et al 2004, Laing et al 2011). In addition, ultrasound exposure has been shown to mediate delivery of therapeutic-loaded ELIP into vascular tissue (Herbst et al 2010, Hitchcock et al 2010).…”