Migration and homing of bone-marrow mononuclear cells in chronic ischemic stroke after intra-arterial injection

Cell-based treatments have been considered a promising therapy for neurological diseases. However, currently there are no clinically available methods to monitor whether the transplanted cells reach and remain in the brain. In this study we investigated the feasibility of detecting the distribution and homing of autologous bone-marrow mononuclear cells (BMMCs) labeled with Technetium-99 m (^99mTc) in a cell-based therapy clinical study for chronic ischemic stroke. Six male patients (ages 24-65 years) with ischemic cerebral infarcts within the middle cerebral artery (MCA) between 59 and 82 days were included. Cell dose ranged from 1.25 × 10⁸ to 5 × 10⁸. Approximately 2 × 10⁷ cells were labeled with ^99mTc and intra-arterially delivered together with the unlabeled cells via a catheter navigated to the MCA. None of the patients showed any complications on the 120-day follow-up. Whole body scintigraphies indicated cell homing in the brain of all patients at 2 h, while the remaining uptake was mainly distributed to liver, lungs, spleen, kidneys and bladder. Moreover, quantification of uptake in Single-Photon Emission Computed Tomography (SPECT) at 2 h showed preferential accumulation of radioactivity in the hemisphere affected by the ischemic infarct in all patients. However, at 24 h homing could only distinguished in the brains of 2 patients, while in all patients uptake was still seen in the other organs. Taken together, these results indicate that labeling of BMMCs with ^99mTc is a safe and feasible technique that allows monitoring the migration and engraftment of intra-arterially transplanted cells for at least 24 h.