Cellular therapeutics have great potential to repair lost tissue and restore function in organs such as the heart. One hurdle to translation though is monitoring the fate of injected cell therapeutics. Tracking the success of cell survival and integration can be challenging as it is difficult to non-invasively differentiate between normal and therapeutically administered cells once injected into the site of injury. Contrast agents localized in cells can aid visualization in deep organs using techniques like magnetic resonance imaging (MRI) but their effect is diluted with cell division. Expression of magnetic proteins, like ferritin, solves this problem but suffers from low sensitivity of detection. Consequently, if improvements in sensitivity can be achieved it would significantly enhance the prospects of research and perhaps even clinical use.
Researchers at the University of Toronto have developed a “bright-contrast” method that can reliably and sensitively track the fate of cellular therapeutics. This technique relies upon the production of two proteins; a metal transporter which is used to pump manganese ions across the cell membrane, whereafter the ions are synthesized into a contrast generating metal ball housed within an organic ferritin cage. The metal nanoparticle produces “bright-contrast” in an MRI instrument.
Figure. Production of the “bright-ferritin” nanoparticle. Manganese ions (red) are transported across the cell membrane by a metal transporter (brown). Assembly of ferritin monomers (grey) enable formation of a MRI contrast-generating metal nanoparticle (red and grey).
- “Bright-contrast” cell-tracking agent for visualization of cells:
- Long-term, real-time tracking
- Deep-tissue imaging
- Non-invasive, non-destructive imaging
- Reduces animal numbers and costs
- Companion imaging modality that provides information on cell survival and localization to aid regulatory submissions for cell therapy platforms
- Focused applications: Neural, cardiac and hepatic regeneration
- Monitor tumorigenesis in pluripotent stem cell therapies
- Time-course information in the same cell therapy recipient
- Tracking of cells for fundamental studies and drug development
INTELLECTUAL PROPERTY STATUS
- Provisional patent filed (Ferritin for Cellular Tracking Utilizing T1-Weighted MRI)
- Proof-of-concept studies have demonstrated the ability to track human cells (HEK293) in mice using MRI. More recent studies have demonstrated the ability to image human embryonic stem cells using “bright-ferritin”.
- Ongoing work for CNS and cardiac applications