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CLINICAL RESEARCH

Magnetically Targeted Endothelial Cell Localization in Stented Vessels

Sorin V. Pislaru, MD, PhD^_*, Adriana Harbuzariu, MD^_*, Rajiv Gulati, MD, PhD^_*, Tyra Witt^_*, Nicole P. Sandhu, MD, PhD, Robert D. Simari, MD, FACC^_* and Gurpreet S. Sandhu, MD, PhD, FACC^_*,_*

^_* Division of Cardiovascular Diseases
Division of General Internal Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota

Manuscript received May 3, 2006; revised manuscript received June 26, 2006, accepted June 26, 2006.

^_* Reprint requests and correspondence: Dr. Gurpreet S. Sandhu, Division of Cardiovascular Diseases, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, Minnesota 55905. (Email: sandhu.gurpreet{at}mayo.edu).

OBJECTIVES: A novel method to magnetically localize endothelial cells at the site of a stented vessel wall was developed. The application of this strategy in a large animal model is described.

BACKGROUND: Local delivery of blood-derived endothelial cells has been shown to facilitate vascular healing in animal models. Therapeutic utilization has been limited by an inability to retain cells in the presence of blood flow. We hypothesized that a magnetized stent would facilitate local retention of superparamagnetically labeled cells.

METHODS: Cultured porcine endothelial cells were labeled with endocytosed superparamagnetic iron oxide microspheres. A 500:1 microsphere-to-cell ratio was selected for in vivo experiments based on bromo-deoxyuridine incorporation and terminal deoxynucleotidyl transferase mediated dUTP nick end labeling assays. Stents were magnetized and implanted in porcine coronary and femoral arteries using standard interventional equipment. Labeled endothelial cells were delivered locally during transient occlusion of blood flow.

RESULTS: The delivered cells were found attached to the stent struts and were also distributed within the adjacent denuded vessel wall at 24 h.

CONCLUSIONS: Magnetic forces can be used to rapidly place endothelial cells at the site of a magnetized intravascular stent. The delivered cells are retained in the presence of blood flow and also spread to the adjacent injured vessel wall. Potential applications include delivering a cell-based therapeutic effect to the local vessel wall as well as downstream tissue.

Abbreviations and Acronyms   BrdU = bromo-deoxyuridine   EOC = endothelial outgrowth cell   MRI = magnetic resonance imaging   SPM = superparamagnetic microsphere   TUNEL = terminal deoxynucleotidyl transferase mediated dUTP nick end labeling

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