In Vivo MRI tracking of bone mesenchymal stem cell viability with a T1-T2 switchable contrast agent

Abstract

The successful implementation of stem cell therapy requires the development of imaging techniques to track transplanted stem cells in vivo and monitor their fate over time. Most in vivo imaging methods focus on providing information about the distribution and migration of transplanted stem cells, while monitoring their viability-crucial for optimizing therapy-remains undeveloped. Although a few in vivo imaging techniques have been developed for assessing the viability of transplanted stem cells, their applicability is restricted by limited penetration depth. To address this, magnetic resonance imaging (MRI) that is collaboratively utilized with tailored contrast agents has been explored to track the viability of transplanted stem cells without this limitation. However, currently available MRI contrast agents struggle with low accuracy in monitoring viability due to poor controllability or minimal signal change in response to cell death. Here, we present an extremely small iron oxide nanoparticles (ESIONPs)-based T₁-T₂ switchable MRI contrast agent (ESIONPs-GSH) designed to accurately detect cell apoptosis in response to elevated reactive oxygen species (ROS).Specifically, ESIONPs-GSH was obtained by modifying the surface of ESIONPs with ROS-sensitive glutathione (GSH) and amphipathic 3-((3-aminopropyl) dimethylammonio) propane-1-sulfonate (ADPS) molecules. The results demonstrate that ESIONPs-GSH is biocompatible, with negligible effects on the proliferation and differentiation of bone mesenchymal stem cells (BMSCs) post-labeling. Additionally, BMSCs labeled with ESIONPs-GSH exhibit T₁ contrast; upon cell death, increasing cellular ROS oxidize GSH and induce cross-linking of ESIONPs-GSH, resulting in a switch to T₂ contrast. Benefiting from the significantly contrasting signal following the T₁-T₂ contrast switch, ESIONPs-GSH allows for accurate assessment of the survival of BMSCs transplanted into the axillary regions of mice through MRI monitoring. ESIONPs-GSH enabled MRI can effectively track transplanted stem cell viability in vivo without penetration depth limitations, making it a promising tool for guiding stem cell-based therapies.