Application of dual 19 F and iron cellular MRI agents to track the infiltration of immune cells to the site of a rejected stem cell transplant.

ABSTRACT

PURPOSE: Cellular MRI) was used to detect implanted human mesenchymal stem cells (hMSCs) and the resulting macrophage infiltration that occurs in response to xenotransplantation. METHODS: Human mesenchymal stem cells were prelabeled with a fluorine-19 (19 F) agent prior to implantation, allowing for their visualization and quantification over time. Following implantation of 1 × 10619 F-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. RESULTS: Quantification of 19 F MRI on day 0 agreed with the implanted number of cells, and 19 F signal decreased over time. By day 14, only 22% ± 11% of the original 19 F signal remained. In a second group, USPIO were administered intravenously after implantation of 19 F-labeled hMSCs. When imaged on day 2, a significant decrease in 19 F 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. CONCLUSION: 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 78713-720, 2017. © 2016 International Society for Magnetic Resonance in Medicine.