Bright Ferritin—a Reporter Gene Platform for On-Demand, Longitudinal Cell Tracking on MRI
Daniel A. Szulc,
Xavier A. Lee,
Hai-Ying Mary Cheng,
Hai-Ling Margaret Cheng
Affiliations
Daniel A. Szulc
Institute of Biomedical Engineering, University of Toronto, 164 College Street, RS407, Toronto, ON M5S 3G9, Canada; Ted Rogers Centre for Heart Research, Translational Biology & Engineering Program, University of Toronto, Toronto, ON M5G 1M1, Canada
Xavier A. Lee
Ted Rogers Centre for Heart Research, Translational Biology & Engineering Program, University of Toronto, Toronto, ON M5G 1M1, Canada; Department of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada
Hai-Ying Mary Cheng
Department of Biology, University of Toronto Mississauga, Mississauga, ON L5L 1C6, Canada
Hai-Ling Margaret Cheng
Institute of Biomedical Engineering, University of Toronto, 164 College Street, RS407, Toronto, ON M5S 3G9, Canada; Ted Rogers Centre for Heart Research, Translational Biology & Engineering Program, University of Toronto, Toronto, ON M5G 1M1, Canada; The Edward S. Rogers Sr. Department of Electrical & Computer Engineering, University of Toronto, Toronto, ON M5S 3G4, Canada; Corresponding author
Summary: A major unresolved challenge in cell-based regenerative medicine is the absence of non-invasive technologies for tracking cell fate in deep tissue and with high spatial resolution over an extended interval. MRI is highly suited for this task, but current methods fail to provide longitudinal monitoring or high sensitivity, or both. In this study, we fill this technological gap with the first discovery and demonstration of in vivo cellular production of endogenous bright contrast via an MRI genetic reporter system that forms manganese-ferritin nanoparticles. We demonstrate this technology in human embryonic kidney cells genetically modified to stably overexpress ferritin and show that, in the presence of manganese, these cells produce far greater contrast than conventional ferritin overexpression with iron or manganese-permeable cells. In living mice, diffusely implanted bright-ferritin cells produce the highest and most sustained contrast in skeletal muscle. The bright-ferritin platform has potential for on-demand, longitudinal, and sensitive cell tracking in vivo.
