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 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.


RESULTS
Peripheral blood mononuclear cells 1-5 × 10(9) 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 10(8) 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 10(9) 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. Clinical Trial Registration- URL: http://www.clinicaltrials.gov; Unique identifier: NCT00972946, NCT01169935.
Centre of Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom . jenny.richards@ed.ac.uk
Jennifer M J
JM
Richards
Catherine A
CA
Shaw
Ninian N
NN
Lang
Michelle C
MC
Williams
Scott I K
SI
Semple
Thomas J
TJ
MacGillivray
Calum
C
Gray
Julie H
JH
Crawford
Shirjel R
SR
Alam
Anne P M
AP
Atkinson
Elaine K
EK
Forrest
Carol
C
Bienek
Nicholas L
NL
Mills
Anne
A
Burdess
Kev
K
Dhaliwal
A John
AJ
Simpson
William A
WA
Wallace
Adam T
AT
Hill
P Huw
PH
Roddie
Graham
G
McKillop
Thomas A
TA
Connolly
Giora Z
GZ
Feuerstein
G Robin
GR
Barclay
Marc L
ML
Turner
David E
DE
Newby
D002465:Cell Movement / Q000187:drug effects; D058948:Cell Tracking / Q000379:methods*; D003287:Contrast Media / Q000737:chemistry / Q000493:pharmacokinetics*; D016207:Cytokines / Q000378:metabolism; D003911:Dextrans / Q000737:chemistry / Q000493:pharmacokinetics*; D005240:Feasibility Studies; D006801:Humans; D007091:Image Processing, Computer-Assisted; D021621:Imaging, Three-Dimensional; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles / Q000737:chemistry; D061214:Patient Safety; D013194:Staining and Labeling; D018709:Statistics, Nonparametric; D014374:Tuberculin Test
D003287:Contrast Media; D016207:Cytokines; D003911:Dextrans; D058185:Magnetite Nanoparticles; C065507:ferumoxides