Abstract
The therapeutic potential of mesenchymal stem cells (MSCs) is limited, as many cells undergo apoptosis following administration. In addition, the attraction of immune cells (predominately macrophages) to the site of implantation can lead to MSC rejection. We implemented a trimodal imaging technique to monitor the fate of transplanted MSCs and infiltrating macrophages in vivo. MSCs were labeled with an iron oxide nanoparticle (ferumoxytol) and then implanted within the hind limb muscle of 10 C57BI/6 mice. Controls received unlabeled MSCs (n = 5). A perfluorocarbon agent was administered intravenously for uptake by phagocytic macrophages in situ; 1 and 12 days later, the ferumoxytol-labeled MSCs were detected by proton (1H) magnetic resonance imaging (MRI) and magnetic particle imaging (MPI). Perfluorocarbon-labeled macrophages were detected by fluorine-19 (19F) MRI. 1H/19F MRI was acquired on a clinical scanner (3 T) using a dual-tuned surface coil and balanced steady-state free precession (bSSFP) sequence. The measured volume of signal loss and MPI signal declined over 12 days, which is consistent with the death and clearance of iron-labeled MSCs. 19F signal persisted over 12 days, suggesting the continuous infiltration of perfluorocarbon-labeled macrophages. Because MPI and 19F MRI signals are directly quantitative, we calculated estimates of the number of MSCs and macrophages present over time. The presence of MSCs and macrophages was validated with histology following the last imaging session. This is the first study to combine the use of iron- and fluorine-based MRI with MPI cell tracking.
Highlights
Mesenchymal stem cells (MSCs) have shown promising results as a cellular therapeutic
Our aim is to combine the use of iron-based magnetic resonance imaging (MRI), 19F MRI, and magnetic particle imaging (MPI) cellular imaging technologies to monitor and quantify the persistence of transplanted MSCs and infiltrating macrophages in vivo
We explored the ability to label, detect, and quantify MSCs with ferumoxytol for detection in 1H MRI and MPI images, and infiltrating macrophages with PFC for 19F MRI detection
Summary
Mesenchymal stem cells (MSCs) have shown promising results as a cellular therapeutic. Several proposed therapies rely on the pleiotropic effects that MSCs impose on their local microenvironment through the release of extracellular vesicles, cytokines, and tropic factors [3,4,5]. MSCs have been shown to exert antimicrobial effects, promote local vascularization and cell growth, and modulate inflammation [1, 2, 6]. Apoptotic stem cells release cytokines that attract immune cells (predominately macrophages) to the implant site. A high influx of these cells can trigger stem-cell rejection [8]. The potential of MSC therapy is limited by MSC death and immune rejection; the development of a technique to TOMOGRAPHY.ORG I VOLUME 5 NUMBER 4 I DECEMBER 2019
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