Magnetic Nanoparticle-Mediated Targeting of Cell Therapy Reduces In-Stent Stenosis in Injured Arteries.
Although drug-eluting stents have dramatically reduced the recurrence of restenosis after vascular interventions, the nonselective antiproliferative drugs released from these devices significantly delay reendothelialization and vascular healing, increasing the risk of short- and long-term stent failure. Efficient repopulation of endothelial cells in the vessel wall following injury may limit complications, such as thrombosis, neoatherosclerosis, and restenosis, through reconstitution of a luminal barrier and cellular secretion of paracrine factors. We assessed the potential of magnetically mediated delivery of endothelial cells (ECs) to inhibit in-stent stenosis induced by mechanical injury in a rat carotid artery stent angioplasty model. ECs loaded with biodegradable superparamagnetic nanoparticles (MNPs) were administered at the distal end of the stented artery and localized to the stent using a brief exposure to a uniform magnetic field. After two months, magnetic localization of ECs demonstrated significant protection from stenosis at the distal part of the stent in the cell therapy group compared to both the proximal part of stent in the cell therapy group and the control (stented, nontreated) group: 1.7-fold (p < 0.001) less reduction in lumen diameter as measured by B-mode and color Doppler ultrasound, 2.3-fold (p < 0.001) less reduction in the ratios of peak systolic velocities as measured by pulsed wave Doppler ultrasound, and 2.1-fold (p < 0.001) attenuation of stenosis as determined through end point morphometric analysis. The study thus demonstrates that magnetically assisted delivery of ECs is a promising strategy for prevention of vessel lumen narrowing after stent angioplasty procedure.
Department of Surgery, Drexel University College of Medicine , Philadelphia, Pennsylvania 19102, United States.|Department of Pharmacology and Physiology, Drexel University College of Medicine , Philadelphia, Pennsylvania 19102, United States.
Boris
B
Polyak
Department of Surgery, Drexel University College of Medicine , Philadelphia, Pennsylvania 19102, United States.
Mikhail
M
Medved
Department of Surgery, Drexel University College of Medicine , Philadelphia, Pennsylvania 19102, United States.
Nina
N
Lazareva
Department of Surgery, Drexel University College of Medicine , Philadelphia, Pennsylvania 19102, United States.|Molecular Cell Biology and Genetics (MCBG) Program, Drexel University College of Medicine , Philadelphia, Pennsylvania 19102, United States.
Lindsay
L
Steele
Department of Surgery, Drexel University College of Medicine , Philadelphia, Pennsylvania 19102, United States.
Tirth
T
Patel
Department of Surgery, Drexel University College of Medicine , Philadelphia, Pennsylvania 19102, United States.
Ahmad
A
Rai
The Avram and Stella Goldstein-Goren Department of Biotechnology Engineering, Ben-Gurion University of the Negev , Beer-Sheva 84105, Israel.
Menahem Y
MY
Rotenberg
Department of Surgery, Drexel University College of Medicine , Philadelphia, Pennsylvania 19102, United States.
Kimberly
K
Wasko
Department of Medicine, Division of Cardiology, Drexel University College of Medicine , Philadelphia, Pennsylvania 19102, United States.
Andrew R
AR
Kohut
Department of Surgery, Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania 19104, United States.
Richard
R
Sensenig
Department of Surgery, Drexel University College of Medicine , Philadelphia, Pennsylvania 19102, United States.|Department of Electrical and Computer Engineering, Drexel University , Philadelphia, Pennsylvania 19104, United States.
Gary
G
Friedman
cell therapy; endothelium; in-stent restenosis; magnetic nanoparticles; magnetic targeting; vascular healing