Tracking of autologous VSOP-labeled mesenchymal stem cells in the sheep brain using 3.0 T MRI

Assessment of biodistribution and monitoring of cell migration processes in vivo are essential for the safety of novel cell-based therapies for ischemic stroke and early-stage clinical trials, but are mainly lacking investigation in large animal models which are closer to the situation found in human patients. This chapter reports a series of experiments which establish a MRI-sensitive labeling procedure for autologous ovine mesenchymal stem cells (MSC) and the assessment of in vivo and in vitro detection limits of the cells at 3.0 T. Cell migration was monitored after intravenous transplantation following experimental stroke in sheep. Cell detection was feasible at 3.0 T with detection limits defined at 500 cells in vitro and 1,000 cells after local stereotaxic administration in vivo. No signs for MSC homing toward the ischemic lesion were observed after systemic cell delivery. Iron-containing cells were identified in the lung and skin wounds, but not in brain parenchyma after intravenous cell delivery. These findings are in contrast to results obtained in small animal models and may indicate significant differences of MSC behavior in large organisms. They also revealed the necessity for sensitivity-enhanced MRI sequences for improved cell detection in large animals