Tracking of HMSCs preconditioned with 0.5% [O.sub.2] in association with stroke utilizing 1H and [sup.23]NA MRI at 21.1 T

As evaluated by ultra-high field ¹H and [sup.23]Na MRI, human mesenchymal stem cells (hMSCs) exposed to 2% [O.sub.2] (hypoxia) have shown enhanced therapeutic effects once transplanted into an ischemic brain. In this study, we further investigate hypoxic preconditioning by using a sublethal exposure, 0.5% [O.sub.2], prior to intra-arterial injection of cells in to a stroked rat brain. Preconditioned hMSCs were transfected with an iron based contrast agent (SPIOs) for cell tracking. Serial MRI at 21.1 T was performed to acquire ¹H and [sup.23]Na images of lesion progression and cell migration. Images of the ischemic stroke [1] lesion show increased signal as evidenced by the influx of extracellular water. Increases in tissue sodium concentration are seen by [sup.23]Na MRI, and the SPIO labeled cells are visualized as signal voids. Histological tissue sections show the localization of the iron-labeled hMSCs in brain tissue. With Na MRI, the sublethal pretreatment showed a trend towards increased stroke recovery compared to normoxic and control; however, statistical significance was not reached. In fact, the 2% hypoxic pre-treatment is the only test group showing a significant difference as evaluated with Na MRI. With the respect to the permanence of the hMSCs, the average decrease is lower for the sublethal cells compared to both the 2% hypoxic pretreatment and to normoxic cells, but again statistical significance was not achieved. In conclusion, this study shows limited benefits for the sublethal pretreatment compared to previous hypoxic protocols.