Tracking the Fate of Stem Cell Implants with Fluorine-19 MRI

Background

In this study we used cellular magnetic resonance imaging (MRI) to detect mesenchymal stem cells (MSC) labeled with a Fluorine-19 (¹⁹F) agent. ¹⁹F-MRI offers unambiguous detection and in vivo quantification of labeled cells.

Methods

We investigated two common stem cell transplant mouse models: an immune competent, syngeneic transplant model and an immune compromised, xenograft transplant model. ¹⁹F labelled stem cells were implanted intramuscularly into the hindlimb of healthy mice. The transplant was then monitored for up to 17 days using ¹⁹F-MRI, after which the tissue was excised for fluorescence microscopy and immunohistochemisty.

Results

Immediately following transplantation, ¹⁹F-MRI quantification correlated very well with the expected cell number in both models. The 19F signal decreased over time in both models, with a more rapid decrease in the syngeneic model. By endpoint, only 2/7 syngeneic mice had any detectable ¹⁹F signal. In the xenograft model, all mice had detectable signal at endpoint. Fluorescence microscopy and immunohistochemistry were used to show that the ¹⁹F signal was related to the presence of bystander labeled macrophages, and not original MSC.

Conclusions

Our results show that ¹⁹F-MRI is an excellent tool for verifying the delivery of therapeutic cells early after transplantation. However, in certain circumstances the transfer of cellular label to other bystander cells may confuse interpretation of the long-term fate of the transplanted cells.