Use of Endothelial Cells Containing Superparamagnetic Microspheres to Improve Endothelial Cell Delivery to Arterial Surfaces after Angioplasty

Abstract

The purpose of this study was to determine if the luminal surface of balloon-dilated arteries can be re-endothelialized circumferentially with use of normal endothelial cells (ECs) and superparamagnetic microsphere-containing endothelial cells (MagECs) to cover gravity-dependent and independent arterial surfaces, respectively. MagECs were obtained after phagocytosis of albumin-coated superparamagnetic polystyrene microspheres by rabbit microvascular ECs. The effect of microsphere internalization on cell adhesion was determined in vitro by comparing ECs and MagECs in terms of time courses of adhesion to fibronectin and cell retention after exposure to a shear stress. In vivo re-endothelialization was performed by delivering fluorescently labeled ECs and MagECs to a balloon-dilated artery with a double-balloon catheter, placing a magnet over the artery, and rotating the rabbit axially. Endoluminal coverage of arterial cross-sections was estimated by epifluorescence microscopy. Under the influence of gravity, in vitro cell adhesion to fibronectin after 5, 10, and 15 minutes was similar for the ECs (34%, 74%, and 70%) and MagECs (40%, 56%, and 93%). In vitro cell retention after exposure to a shear stress (25 dynes/cm2) was greater (P < .05) for ECs than for MagECs (82% vs 69%). Use of ECs plus MagECs in vivo resulted in cell delivery that was nearly circumferential. Delivery of a mixture of ECs and MagECs in combination with animal rotation and a magnetic field provide nearly circumferential delivery of ECs to the luminal surface of balloon-dilated arteries. The presence of superparamagnetic microspheres in cells does not impede cell adhesion but does decrease cell retention after exposure to a fluid shear.