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Magnetic Tagging Increases Delivery of Circulating Progenitors in Vascular Injury

Panagiotis G. Kyrtatos, BMedSci^_*,,, Pauliina Lehtolainen, PhD^_*, Manfred Junemann-Ramirez, MD, Ana Garcia-Prieto, PhD^||, Anthony N. Price, PhD^_*, John F. Martin, MD, David G. Gadian, DPhil, Quentin A. Pankhurst, PhD^,||, Mark F. Lythgoe, PhD^_*,,_*

^_* Centre for Advanced Biomedical Imaging, University College London (UCL) Department of Medicine and UCL Institute of Child Health, London, United Kingdom
Radiology and Physics Unit, UCL Institute of Child Health, London, United Kingdom
Centre for Cardiovascular Biology and Medicine, UCL Department of Medicine, London, United Kingdom
Davy-Faraday Research Laboratories, The Royal Institution of Great Britain, London, United Kingdom
^|| London Centre for Nanotechnology, London, United Kingdom

^_* Reprint requests and correspondence: Dr. Mark Lythgoe, Centre for Advanced Biomedical Imaging, University College London, 72 Huntley Street, WC1E 6DD London, United Kingdom (Email: mlythgoe{at}ich.ucl.ac.uk).

Objectives: We sought to magnetically tag endothelial progenitor cells (EPCs) with a clinical agent and target them to a site of arterial injury using a magnetic device positioned outside the body.

Background: Circulating EPCs are involved in physiological processes such as vascular re-endothelialization and post-ischemic neovascularization. However, the success of cell therapies depends on the ability to deliver the cells to the site of injury.

Methods: Human EPCs were labeled with iron oxide superparamagnetic nanoparticles. Cell viability and differentiation were tested using flow cytometry. Following finite element modeling computer simulations and flow testing in vitro, angioplasty was performed on rat common carotid arteries to denude the endothelium and EPCs were administered with and without the presence of an external magnetic device for 12 min.

Results: Computer simulations indicated successful external magnetic cell targeting from a vessel with flow rate similar to a rat common carotid artery; correspondingly there was a 6-fold increase in cell capture in an in vitro flow system. Targeting enhanced cell retention at the site of injury by 5-fold at 24 h after implantation in vivo.

Conclusions: Using an externally applied magnetic device, we have been able to enhance EPC localization at a site of common carotid artery injury. This technology could be more widely adapted to localize cells in other organs and may provide a useful tool for the systemic injection of cell therapies.

Key Words: endothelial cells • local delivery • magnet • targeting • angioplasty

Abbreviations and Acronyms   CCA = common carotid artery   EPC = endothelial progenitor cell   FDA = Food and Drug Administration   MNC = mononuclear cell   MRI = magnetic resonance imaging/images   SPIO = superparamagnetic iron oxide

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