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目的评价人骨髓间充质干细胞脑内移植对食蟹猴脑出血模型的治疗作用。方法符合普通级标准的成年食蟹猴12只,用自体股动脉抗凝血脑内注射方法建模后1周,用脑立体定位法在血肿周围植入人骨髓间充质干细胞,细胞数分别为高剂量5×106、低剂量1×106、对照组等体积生理盐水。利用MRI、PET、神经功能缺损评分和组织病理学对干细胞移植效果进行评价。结果神经功能评分显示干细胞移植1周后动物神经功能明显改善。PET结果显示干细胞移植后2周高剂量组血肿周围皮层、基底节核团的SUV%值与对照组间存在显著性差异(P=0.02)。移植后3周高、低剂量组血肿周围皮层、基底节核团的SUV%值与对照组间差异存在显著性(P值分别为0.03和0.04)。MRI显示剂量组血肿吸收速度大于对照组。病理检查可见剂量组坏死灶面积小于对照组,出血灶周围有大量新生血管生成,剂量组与对照组间差异存在显著性(P<0.01)。结论在损伤脑组织周围移植hBMSC可促进食蟹猴损伤神经组织的恢复,为hBMSC治疗脑出血的临床应用提供了重要实验依据。
Objective To evaluate the therapeutic effect of intracerebral transplantation of human bone marrow mesenchymal stem cells on cerebral hemorrhage in cynomolgus monkeys. Methods Twelve adult cynomolgus monkeys, who met the general standard, were implanted with human bone marrow mesenchymal stem cells around the hematoma by brain stereotactic method 1 week after modeling by intracapsular injection of autologous femoral artery. For the high dose of 5 × 106, low dose of 1 × 106, the control group of equal volume of saline. The effect of stem cell transplantation was evaluated using MRI, PET, neurological deficit score and histopathology. Results The neurological score showed that the neurological function of animals improved significantly after 1 week of stem cell transplantation. The results of PET showed that there was a significant difference (P = 0.02) between the SUV% values of the cortex and basal ganglia in the high-dose group at 2 weeks after stem cell transplantation compared with the control group. At 3 weeks after transplantation, there was a significant difference (P = 0.03 and 0.04, respectively) between the SUV% values of the cortex and basal ganglia in the high and low dose groups compared with the control group. MRI showed that the dose group hematoma absorption rate is greater than the control group. Pathological examination shows that the area of necrotic lesions in the dose group is smaller than that in the control group, and there are a large number of neovascularization around the hemorrhagic lesions. There is significant difference between the dose group and the control group (P <0.01). Conclusion Transplantation of hBMSCs around injured brain tissue can promote the recovery of injured cynomolgus nerve tissue and provide an important experimental basis for the clinical application of hBMSC in the treatment of cerebral hemorrhage.