In Vivo Mononuclear Cell Tracking Using Superparamagnetic Particles of Iron Oxide: Feasibility and Safety in Humans
Background—Cell therapy is an emerging and exciting novel treatment option for cardiovascular disease that relies upon the delivery of functional cells to their target site. Monitoring and tracking cells to ensure tissue delivery and engraftment is a critical step in establishing clinical and therapeutic efficacy. The study aims were (i) to develop a Good Manufacturing Practice (GMP) compliant method of labeling competent peripheral blood mononuclear cells (PBMC) with superparamagnetic particles of iron oxide (SPIO), and (ii) to evaluate its potential for magnetic resonance cell tracking in humans.
Methods and Results—1-5×109 PBMC were labeled with SPIO. SPIO-labeled cells had similar in vitro viability, migratory capacity and pattern of cytokine release to unlabeled cells. Following intramuscular administration, up to 108 SPIO-labeled cells were readily identifiable in vivo for at least 7 days using MRI. Using a phased-dosing study, we demonstrated that systemic delivery of up to 109 SPIO-labeled cells in humans is safe, and cells accumulating in the reticulo-endothelial system were detectable on clinical MRI. In a healthy volunteer model, a focus of cutaneous inflammation was induced in the thigh by intradermal injection of tuberculin. Intravenously-delivered SPIO-labeled cells tracked to the inflamed skin and were detectable on MRI scanning. Prussian blue staining of skin biopsies confirmed iron-laden cells in the inflamed skin.
Conclusions—Human PBMC can be labeled with SPIO without affecting their viability or function. SPIO-labeling for magnetic resonance cell tracking is a safe and feasible technique that has major potential for a range of cardiovascular applications including monitoring of cell therapies and tracking of inflammatory cells.
- Received January 6, 2012.
- Accepted May 31, 2012.
- Copyright © 2012, American Heart Association, Inc. All rights reserved. Unauthorized use prohibited