Magnetic tagging increases delivery of circulating progenitors in vascular injury.
OBJECTIVE
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.
Kyrtatos
Panagiotis G
PG
Centre for Advanced Biomedical Imaging, University College London Department of Medicine and UCL Institute of Child Health, London, United Kingdom.
Lehtolainen
Pauliina
P
Junemann-Ramirez
Manfred
M
Garcia-Prieto
Ana
A
Price
Anthony N
AN
Martin
John F
JF
Gadian
David G
DG
Pankhurst
Quentin A
QA
Lythgoe
Mark F
MF
D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D017209:Apoptosis; D020212:Carotid Artery Injuries / Q000473:pathology / Q000601:surgery*; D002454:Cell Differentiation; D002465:Cell Movement; D002470:Cell Survival; D002478:Cells, Cultured; D003198:Computer Simulation; D003911:Dextrans; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000276:immunology / Q000637:transplantation*; D005240:Feasibility Studies; D052203:Ferrosoferric Oxide; D020342:Finite Element Analysis; D005434:Flow Cytometry; D006023:Glycoproteins / Q000032:analysis; D006801:Humans; D008280:Magnetics; D058185:Magnetite Nanoparticles; D008297:Male; D018613:Microscopy, Confocal; D008955:Models, Cardiovascular; D053758:Nanoparticles; D010455:Peptides / Q000032:analysis; D010865:Pilot Projects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013194:Staining and Labeling / Q000379:methods*; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000276:immunology; D013997:Time Factors
D000071916:AC133 Antigen; D015703:Antigens, CD; D003911:Dextrans; D006023:Glycoproteins; D058185:Magnetite Nanoparticles; D010455:Peptides; C065507:ferumoxides; D052203:Ferrosoferric Oxide