Magnetic Resonance Imaging of Ferumoxide-Labeled Mesenchymal Stem Cells in Cartilage Defects: In Vitro and in Vivo Investigations

Abstract

The purpose of this study was to (1) compare three different techniques for ferumoxide labeling of mesenchymal stem cells (MSCs), (2) evaluate if ferumoxide labeling allows in vivo tracking of matrix-associated stem cell implants (MASIs) in an animal model, and (3) compare the magnetic resonance imaging (MRI) characteristics of ferumoxide-labeled viable and apoptotic MSCs. MSCs labeled with ferumoxide by simple incubation, protamine transfection, or Lipofectin transfection were evaluated with MRI and histopathology. Ferumoxide-labeled and unlabeled viable and apoptotic MSCs in osteochondral defects of rat knee joints were evaluated over 12 weeks with MRI. Signal to noise ratios (SNRs) of viable and apoptotic labeled MASIs were tested for significant differences using t-tests. A simple incubation labeling protocol demonstrated the best compromise between significant magnetic resonance signal effects and preserved cell viability and potential for immediate clinical translation. Labeled viable and apoptotic MASIs did not show significant differences in SNR. Labeled viable but not apoptotic MSCs demonstrated an increasing area of T2 signal loss over time, which correlated to stem cell proliferation at the transplantation site. Histopathology confirmed successful engraftment of viable MSCs. The engraftment of iron oxide–labeled MASIs by simple incubation can be monitored over several weeks with MRI. Viable and apoptotic MASIs can be distinguished via imaging signs of cell proliferation at the transplantation site.

Fluorescence molecular tomography of DiR-labeled mesenchymal stem cell implants for osteochondral defect repair in rabbit knees

“…In the literature, most studies with mesenchymal stem cells labelled with a contrast agent made use of even higher cell numbers for imaging [7,52,53]. We assume that the authors thus tried to reach a significantly stronger contrast effect for imaging evaluation.…”

“…Stem cell labelling and tracking techniques with clinically applicable MR contrast agents are already established without impairment of cell viability or differentiation capacity [7,41]. Optical fluorescence imaging as a non-ionizing, fast, and costefficient imaging modality has also been considered in planar mode for the evaluation and monitoring of labelled cells [42,43].…”

“…MR imaging is the preferred technique compared to CT as it combines high anatomical resolution with high soft tissue contrast without radiation exposure [5]. MR imaging allows for non-invasive evaluation of labelled cells [6] and cell implants in osteochondral defects [7]. However, it is aggravated by imaging artefacts through bone and tissue heterogeneity [8] and inherently limited in its ability to assess cortical bone at high spatial resolution.…”

Intravenous Ferumoxytol Allows Noninvasive MR Imaging Monitoring of Macrophage Migration into Stem Cell Transplants

“…Our MR imaging approach could indirectly depict failed, apoptotic stem cell implants by depicting influx of ironlabeled macrophages into MASIs. This approach is closer to potential clinical applications than direct labeling of stem cells with iron oxides, as previously performed by our group and others (41)(42)(43)(44). In addition, direct iron oxide labeling provided limited information about the viability of the transplanted cells (41).…”

Magnetic resonance imaging monitoring dual-labeled stem cells for treatment of mouse nerve injury

“…Moreover, MRI allows repetitive investigations without known side effects and without risk of radiotoxic damage to the transplanted cells (17). Superparamagnetic iron oxide nanoparticles (SPIONs) have been used as targeted or molecular probes for many years to improve the image contrast in MRI (18,19). These advantages are promising for tracking stem cell transplantation during the repair of peripheral nerve injury in vivo.…”