Serial 18F-FDG PET Demonstrates Benefit of Human Mesenchymal Stem Cells in Treatment of Intracerebral Hematoma: A Translational Study in a Primate Model
Serial 18F-FDG PET Demonstrates Benefit of Human Mesenchymal Stem Cells in Treatment of Intracerebral Hematoma: A Translational Study in a Primate Model
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DOI：
10.2967/jnumed.110.080325
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发表时间：
2011-01-01
影响因子：
9.3
通讯作者：
Wang, Renzhi
中科院分区：
文献类型：
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作者：
Feng, Ming;Zhu, Hua;Wang, Renzhi
本研究使用灵长类动物模型和系列F-18-FDG PET扫描评估了人间充质干细胞（hMSCs）治疗脑内血肿（ICH）的疗效。方法：入组24只食蟹猴（雄性，4.2 +/- 0.2 kg）。脑出血模型的建立采用立体定向引导在右侧皮质和基底节之间注射1.5 mL自体动脉血。在脑出血后1周（早期治疗组，n = 8）或4周（晚期治疗组，n = 8），使用立体定向方法将（1-5）× 10（6）hMSCs移植到血肿附近。对照猴在ICH建立后1或4周（每个亚组n = 4）仅接受生理盐水。每周或每两周通过连续F-18-FDG PET扫描（n = 19）和神经功能缺损评分评价治疗效果。hMSC移植后8 wk进行病理学分析。结果如下：在hMSC注射后一周，在早期和晚期hMSC治疗组中，在同侧基底神经节处积累更高的F-18-FDG，表明对治疗的早期反应。当恢复达到平台期时，早期治疗组邻近皮质的F-18-FDG摄取显著高于对照组（P < 0.05）。hMSC治疗组的神经功能缺损评分显著较低，这也表明恢复更好。病理学分析显示hMSC治疗组血肿周围血管密度较高。结论：这项初步研究表明，在灵长类动物模型中，hMSCs移植可能会改善ICH的恢复，早期治疗可能会导致更好的结果。
This study evaluated the efficacy of human mesenchymal stem cells (hMSCs) in the treatment of intracerebral hematoma (ICH) using a primate model and serial F-18-FDG PET scans. Methods: 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) x10(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 F-18-FDG PET scans (n = 19) and neurologic deficit scoring weekly or biweekly. Pathologic analysis was performed 8 wk after hMSC transplantation. Results: One week after hMSC injection, higher F-18-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, F-18-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. Conclusion: 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.