Application of dual19F and iron cellular MRI agents to track the infiltration of immune cells to the site of a rejected stem cell transplant.
Cellular MRI) was used to detect implanted human mesenchymal stem cells (hMSCs) and the resulting macrophage infiltration that occurs in response to xenotransplantation.



Human mesenchymal stem cells were prelabeled with a fluorine-19 (19F) agent prior to implantation, allowing for their visualization and quantification over time. Following implantation of 1 × 10619F-labeled hMSCs into the mouse hind limb, longitudinal imaging was performed to monitor the stem cell graft. Macrophages were labeled in situ by the intravenous administration of an ultrasmall superparamagentic iron oxide (USPIO), allowing for tracking of the inflammatory response.



Quantification of19F MRI on day 0 agreed with the implanted number of cells, and19F signal decreased over time. By day 14, only 22% ± 11% of the original19F signal remained. In a second group, USPIO were administered intravenously after implantation of19F-labeled hMSCs. When imaged on day 2, a significant decrease in19F signal was observed compared to the first group alongside a large signal void region in the corresponding proton images. Immunohistochemistry confirmed the presence of iron-labeled macrophages in the stem cell tract.



A dual-labeling technique was used to noninvasively track two distinct cell populations simultaneously. This information could be used to provide additional insight into the cause of graft failure. Magn Reson Med 78:713-720, 2017. © 2016 International Society for Magnetic Resonance in Medicine.
Imaging Research Laboratories, Robarts Research Institute, London, Ontario, Canada.|Department of Medical Biophysics, University of Western Ontario, London, Ontario, Canada.
Jeffrey M
JM
Gaudet
Imaging Research Laboratories, Robarts Research Institute, London, Ontario, Canada.
Amanda M
AM
Hamilton
Imaging Research Laboratories, Robarts Research Institute, London, Ontario, Canada.
Yuanxin
Y
Chen
Imaging Research Laboratories, Robarts Research Institute, London, Ontario, Canada.|Department of Medical Biophysics, University of Western Ontario, London, Ontario, Canada.
Matthew S
MS
Fox
Imaging Research Laboratories, Robarts Research Institute, London, Ontario, Canada.|Department of Medical Biophysics, University of Western Ontario, London, Ontario, Canada.
Paula J
PJ
Foster
D000818:Animals; D058948:Cell Tracking / Q000379:methods*; D005461:Fluorine / Q000032:analysis / Q000737:chemistry* / Q000378:metabolism; D006084:Graft Rejection / Q000000981:diagnostic imaging*; D006614:Hindlimb / Q000378:metabolism; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles / Q000032:analysis / Q000737:chemistry*; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000737:chemistry / Q000166:cytology; D051379:Mice
D058185:Magnetite Nanoparticles; D005461:Fluorine
19F-MRI, fluorine-19; cellular MRI; mesenchymal stem cells; transplant rejection