人骨髓间充质干细胞移植对食蟹猴脑出血模型损伤的修复作用

目的观察人骨髓间充质干细胞（human mesenchymal stem cells,hMSCs）移植4周和8周后,对食蟹猴脑出血模型脑组织损伤的修复作用。方法在脑定位仪定位下,通过自体血注入法制成食蟹猴脑出血模型,并将其随机分为高剂量治疗组、低剂量治疗组和模型组,分别在脑出血部位附近注入高、低密度的hMSCs和生理盐水。应用整体病理切片扫描、HE染色及免疫组织化学的方法观察hMSCs移植治疗食蟹猴脑出血4周和8周后脑损伤部位的病理变化。结果脑出血模型组可见脑出血损伤部位脑组织大面积变性坏死,多量吞噬含铁血黄素的泡沫细胞增生,周围少许肉芽组织增生伴局部纤维组织形成。hMSCs治疗组,整体切片扫描结果提示,与模型组相比,hMSCs低剂量及高剂量治疗组均可见脑组织变性坏死范围减小,且低剂量治疗组略好于高剂量治疗组;HE染色可见大脑注射部位局部脑组织变性坏死、吞噬含铁血黄素的泡沫细胞增生,周围肉芽组织增生伴局部纤维组织形成。免疫组化发现治疗组出血区内可见神经巢蛋白（Nestin）阳性细胞内散在分布,而在模型组中呈阴性表达。结论hMSCs可促进食蟹猴脑出血脑组织损伤的修复,且治疗效果可能与治疗剂量有一定相关性。

Reparation of Human Mesenchymal Stem Cells on Cynomlgus Macaque with Intracerebral Hemorrhage

Objective To study the reparation effect of intracerebral hemorrhage injury in cynomlgus macaque at the time of 4 and 8 weeks after the transplantation of human mesenchymal stem cells（hMSCs）.Methods With stereotaxic apparatus,the intracerebral hemorrhage models of cynomlgus macaque were established by autologous blood injection,and they were divided into 3 groups randomly（high-dose treatment group,low-dose treatment group and model group）.High,low concentration of hMSCs and normal saline were injected into the vicinity of intracerebral hemorrhage area respectively.4 and 8 weeks after the transplantation,the pathological changes of intracerebral hemorrhage was studied by methods of whole scanning section,HE staining and immunohistochemistry.Results In model group,degeneration and necrosis of brain tissue was evident in the brain injection region.Hyperplasia of foam cells phagocytosed hemosiderin occurred,together with local granulation tissue and fibrous tissue around it.Compared with model group,the area of degeneration and necrosis of brain tissue reduced in both the high-dose treatment group and the low-dose treatment group.Moreover,the injury area of low-dose treatment group was less than that of high-dose treatment group.Local degeneration and necrosis of brain tissue was observed in the brain injection region in treatment group.Hyperplasia of moderate foam cells phagocytosed hemosiderin was found,together with granulation tissue and local fibrous tissue around it.The result of immunohistochemistry showed that there were some nestin-positive cells in intracerebral hemorrhage areas of the treatment groups.No nestin-positive cells were observed in the model group.Conclusion Brain injury reparation can be promoted after the treatment of hMSCs transplantation on cynomlgus macaque with intracerebral hemorrhage and the efficacy of treatment may be associated with treatment dose.