In Vivo Mononuclear Cell Tracking Using Superparamagnetic Particles of Iron Oxide: Feasibility and Safety in Humans

Jennifer M J Richards, Catherine A Shaw, Ninian N Lang, Michelle C Williams, Scott I K Semple, Thomas J MacGillivray, Calum Gray, Julie H Crawford, Shirjel R Alam, Anne P M Atkinson, Elaine K Forrest, Carol Bienek, Nicholas L Mills, Anne Burdess, Kevin Dhaliwal, A John Simpson, William Wallace, Adam T Hill, P Huw Roddie, Graham McKillopThomas A Connolly, Giora Z Feuerstein, G Robin Barclay, Marc L Turner, David E Newby

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.

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.

Clinical Trial Registration
URL:; Unique identifier: NCT00972946, NCT01169935.
Original languageEnglish
Pages (from-to)509-517
Number of pages9
JournalCirculation: Cardiovascular Imaging
Issue number4
Publication statusPublished - Jul 2012

Keywords / Materials (for Non-textual outputs)

  • inflammation
  • macrophages
  • magnetic resonance imaging


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