Serial 18F-FDG PET demonstrates benefit of human mesenchymal stem cells in treatment of intracerebral hematoma: a translational study in a primate model.

Abstract

This study evaluated the efficacy of human mesenchymal stem cells (hMSCs) in the treatment of intracerebral hematoma (ICH) using a primate model and serial 18F-FDG PET scans. Twenty-four Macaca fascicularis monkeys (male, 4.2±0.2 kg) were enrolled. The ICH models were established using a stereo-guided injection of 1.5 mL of autologous arterial blood between the right cortex and basal ganglia. One week (early treatment group, n=8) or 4 wk (late treatment group, n=8) after an ICH was established, (1-5)×10(6) hMSCs were transplanted near the hematoma using a stereotactic method. Control monkeys received saline only, either 1 or 4 wk (n=4 for each subgroup) after ICH establishment. The efficacy of treatment was evaluated by serial 18F-FDG PET scans (n=19) and neurologic deficit scoring weekly or biweekly. Pathologic analysis was performed 8 wk after hMSC transplantation. One week after hMSC injection, higher 18F-FDG accumulated at the ipsilateral basal ganglia in both early and late hMSC-treated groups, indicating an early response to the treatment. When recovery reached a plateau, 18F-FDG uptake in the adjacent cortex was significantly higher in the early treatment group (P<0.05). The neurologic deficit scoring was significantly lower in the hMSC-treated groups, which also indicated better recovery. Pathologic analysis revealed higher vessel density surrounding the remains of hematoma in the hMSC-treated groups. This preliminary study indicates that transplantation of hMSCs may improve the recovery from ICH in a primate model, and early treatment may lead to better results.