Novel MRI Contrast from Magnetotactic Bacteria to Evaluate In Vivo Stem Cell Engraftment

Although human induced pluripotent stem cells (iPSCs) and their derivatives have great potential for the treatment of heart failure. The therapeutic benefit is limited by translational challenges of stem cells such as cell engraftment. Thus, a robust in vivo imaging technology is indispensable to advance the clinical implementation of stem cell therapy. While no available imaging technology meets the requirement for in vivo stem cell tracking, MRI is a highly promising tool due to its high spatial resolution, temporal resolution, and tissue contrast; yet, this modality lacks sensitivity. Superparamagnetic iron oxide particles (SPIONs) addresses this critical imaging issue and have been used as an MRI contrast agent for stem cell tracking. However, their critical limitation is the inability to evaluate cell viability as SPIONs remain in the tissue long after the death of transplanted cells. To address this shortcoming of SPIONs, the novel magneto-endosymbiont-based (MEs) contrast agent was developed (Magnelle^®, Bell Biosystems, Inc., South SF, CA). The MEs utilize the magnetosome biosynthesized by magnetotactic bacteria (MTB), a specific intracellular structure containing inorganic magnetic iron crystals (magnetite or greigite). Having superparamagnetic property like SPIONs, MEs can be detected on T2* weighted imaging. MEs have high safety profile and do not interfere with the functions of transfected cells. Unlike SPIONs, the antiginecity of the MEs are readily recognized and removed from macrophages quickly after the death of labeled cells, eliminating signals from dead cells. In the previous study from our group, iPSC derived cardiomyocytes were labeled with MEs and detected successfully on MRI after transplantation into the heart. In vivo ME signals corresponded with luciferase-based bioluminescence imaging (BLI) of the transplanted cell viability. In conclusion, ME is a novel MRI contrast agent for in vivo cellular tracking that allows accurate longitudinal visualization of the engrafted cells.