SPIO标记脂肪干细胞移植治疗大鼠脑梗死的磁共振示踪成像研究

In vivo MR tracking imaging of SPIO-labeled adipose-derived stem cells transplantation in rat models of brain infarction

目的通过采用多聚左旋赖氨酸(PLL)与超顺磁氧化铁纳米微粒(SPIO)的复合物对脂肪干细胞(ADSCs)体外进行标记,观察SPIO标记ADSCs脑内移植治疗大鼠脑梗死的分布和迁徙情况。方法显微镜下直接结扎大脑中动脉方法制备大鼠脑梗死模型36只,随机分成缺血未干预对照组(12只)、磁性标记ADSCs移植组(12只)和未磁性标记ADSCs移植组(12只),采用立体定向方法脑内移植。对移植后大鼠的神经系统行为和运动功能进行评估,病理组织化学染色观察ADSCs在体内的分布情况,并用磁共振成像的方法在体观察ADSCs的分布,并与病理结果进行对比。结果移植后3周神经系统行为学评分显示移植组动物明显改善,ADSCs脑内移植后3周MRT2WI显示移植区低信号改变并通过胼胝体向病灶迁移。病理组织检查显示磁共振低信号改变区可见普鲁士蓝染色阳性细胞。结论移植ADSCs可以有效地促进大鼠脑梗死后神经行为功能的恢复,MRI可用于在体评价经SPIO和PLL复合物标记的ADSCs细胞移植后在体内的分布、迁移过程。

Objective： To label adipose-derived stem cells （ADSCs） by complex of superparamagnetic iron oxide （SPIO） with poly-L-Lysine （PLL） and to investigate the distribution and migration of ADSCs in rat model of ischemia brain injury. Materials and Methods： The ligation of middle cerebral artery under microscope was used to cause focal brain infarction in rats. ADSCs labeled with SPIO were grafted stereotactically into the contralateral cerebral hemisphere. All animals were randomly divided into control group （n=12）, SPIO-labeled ADSCs group （n=12） and SPIO-unlabeled ADSCs group （n=12）. The neurological severity score （NSS） was used to evaluate neurological function recovery of rats at definite time following the transplantation. The transplanted ADSCs were analyzed in recipient rat brains by pathological method. The biodistribution of grafted ADSCs was monitored noninvasively by MR imaging. Results： Significant improvement in NSS was observed in rats receiving ADSCs transplantation compared with control group after 3 weeks （P〈0.05）. The transplanted ADSCs preferentially engrafted migrated toward the injured brain through callosum. MR imaging showed remarkable hypointense signal in the region of transplantation site, callosum and the rim of infarction especially in T2WI, T2 gradient-recalled echo sequence. Conclusion： Neurological and functional improvement was observed in rats with ADSCs transplantation following iscbemia brain injury. In vivo MR tracking of SPIO-PPL complex labeled ADSCs could evaluate the therapeutic effect and visualize the distribution and migration of SPIO-labeled ADSCs following transplantation.