In vivo mononuclear cell tracking using superparamagnetic particles of iron oxide: feasibility and safety in humans

Richards, J. M.J. et al. (2012) In vivo mononuclear cell tracking using superparamagnetic particles of iron oxide: feasibility and safety in humans. Circulation: Cardiovascular Imaging, 5(4), pp. 509-517. (doi: 10.1161/CIRCIMAGING.112.972596) (PMID:22787016)

Abstract

Background: Cell therapy is an emerging and exciting novel treatment option for cardiovascular disease that relies on 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 (1) to develop a Good Manufacturing Practice–compliant method of labeling competent peripheral blood mononuclear cells with superparamagnetic particles of iron oxide (SPIO), and (2) to evaluate its potential for magnetic resonance cell tracking in humans. Methods and Results: Peripheral blood mononuclear cells 1–5×109 were labeled with SPIO. SPIO-labeled cells had similar in vitro viability, migratory capacity, and pattern of cytokine release to unlabeled cells. After intramuscular administration, up to 108 SPIO-labeled cells were readily identifiable in vivo for at least 7 days using magnetic resonance imaging scanning. 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 reticuloendothelial system were detectable on clinical magnetic resonance imaging. 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 magnetic resonance imaging. Prussian blue staining of skin biopsies confirmed iron-laden cells in the inflamed skin. Conclusions: Human peripheral blood mononuclear cells 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.

• Item Type: Articles
• Additional Information: Sources of funding: This work was supported by an award from the Translational Medicine Research Collaboration. Drs Newby (CH/09/002), Richards (FS/07/060), and Semple (Centre of Research Excellence Award) were supported by the British Heart Foundation. The Wellcome Trust Clinical Research Facility and the Clinical Research Imaging Centre were supported by NHS Research Scotland through NHS Lothian.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Newby, Professor David and Lang, Professor Ninian
• Authors: Richards, J. M.J., Shaw, C. A., Lang, N. N., Williams, M. C., Semple, S. I.K., MacGillivray, T. J., Gray, C., Crawford, J. H., Alam, S. R., Atkinson, A. P.M., Forrest, E. K., Bienek, C., Mills, N. L., Burdess, A., Dhaliwal, K., Simpson, A. J., Wallace, W. A., Hill, A. T., Roddie, P. H., McKillop, G., Connolly, T. A., Feuerstein, G. Z., Barclay, R., Turner, M. L., and Newby, D. E.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Circulation: Cardiovascular Imaging
• Publisher: American Heart Association
• ISSN: 1941-9651
• ISSN (Online): 1942-0080
• Published Online: 01 July 2012