Directing cell therapy to anatomic target sites in vivo with magnetic resonance targeting.
Cell-based therapy exploits modified human cells to treat diseases but its targeted application in specific tissues, particularly those lying deep in the body where direct injection is not possible, has been problematic. Here we use a magnetic resonance imaging (MRI) system to direct macrophages carrying an oncolytic virus, Seprehvir, into primary and metastatic tumour sites in mice. To achieve this, we magnetically label macrophages with super-paramagnetic iron oxide nanoparticles and apply pulsed magnetic field gradients in the direction of the tumour sites. Magnetic resonance targeting guides macrophages from the bloodstream into tumours, resulting in increased tumour macrophage infiltration and reduction in tumour burden and metastasis. Our study indicates that clinical MRI scanners can not only track the location of magnetically labelled cells but also have the potential to steer them into one or more target tissues.
Departments of Infection and Immunity, University of Sheffield, Sheffield S102RX, UK.
Munitta
M
Muthana
Department of Psychology, University of Sheffield, Sheffield S102RX, UK.
Aneurin J
AJ
Kennerley
Department of Oncology, University of Sheffield, Sheffield S102RX, UK.
Russell
R
Hughes
Departments of Infection and Immunity, University of Sheffield, Sheffield S102RX, UK.
Ester
E
Fagnano
Departments of Infection and Immunity, University of Sheffield, Sheffield S102RX, UK.
Jay
J
Richardson
Departments of Infection and Immunity, University of Sheffield, Sheffield S102RX, UK.
Melanie
M
Paul
Unit of Oral &Maxillofacial Medicine &Surgery, University of Sheffield, Sheffield S102RX, UK.
Craig
C
Murdoch
Departments of Infection and Immunity, University of Sheffield, Sheffield S102RX, UK.
Fiona
F
Wright
Centre for Advanced Biomedical Imaging, Division of Medicine, University College London, London WC1E 6DD, UK.
Christopher
C
Payne
Centre for Advanced Biomedical Imaging, Division of Medicine, University College London, London WC1E 6DD, UK.
Mark F
MF
Lythgoe
Institute for Science and Technology in Medicine, Keele University, Stoke-on-Trent ST4 7QB, UK.
Neil
N
Farrow
Department of Biomedical Engineering, University of Florida, Gainesville, Florida 32611, USA.
Jon
J
Dobson
Virttu Biologics, Glasgow, Glasgow City G51 4TF, UK.
Joe
J
Conner
Cardiovascular Sciences, University of Sheffield, Sheffield S102RX, UK.
Jim M
JM
Wild
Department of Oncology, University of Sheffield, Sheffield S102RX, UK.
Claire
C
Lewis
D000818:Animals; D002199:Capillary Permeability; D064987:Cell- and Tissue-Based Therapy; D002478:Cells, Cultured; D003287:Contrast Media; D005290:Ferric Compounds / Q000008:administration & dosage*; D019786:Gadolinium DTPA; D006801:Humans; D008264:Macrophages / Q000502:physiology*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D053768:Metal Nanoparticles / Q000008:administration & dosage*; D051379:Mice; D009374:Neoplasms, Experimental / Q000628:therapy; D050504:Oncolytic Viruses; D011471:Prostatic Neoplasms / Q000628:therapy*; D011897:Random Allocation; D014183:Transplantation, Heterologous
D003287:Contrast Media; D005290:Ferric Compounds; C000499:ferric oxide; D019786:Gadolinium DTPA