磁共振活体监测大鼠间充质干细胞移植治疗急性肾功能衰竭

Magnetic resonance imaging of mesenchymal stem cells transplanted intravascularly in treatment of acute renal failure：in vivo experiment with rats

目的磁共振活体监测移植入急性肾功能衰竭（ARF）大鼠腹主动脉的磁标记间充质干细胞（MSCs）并检测大鼠肾功能及肾脏病理改变。方法磁性纳米粒子体外标记大鼠骨髓MSCs。ARF大鼠分为3组，插导管至腹主动脉，分别移植入标记细胞（10只）；移植入未标记细胞（10只）；灌注等量生理盐水（10只）。移植后0．5h及第1、2、5天应用MRI对移植细胞进行活体示踪，并与肾脏普鲁士蓝染色及CD68抗体染色对照。监测大鼠肾功能恢复及肾脏病理变化情况。结果Fe2O3-PLL可有效标记大鼠MSCs。标记细胞移植后ARF大鼠肾脏皮质区T2＊WI信号强度明显下降，持续到移植后第5天。组织学分析见标记细胞分布于肾皮质肾小球内。细胞移植组肾功能优于对照组，肾损伤程度明显轻于对照组。结论临床应用型1．5T磁共振仪可活体监测移植入ARF大鼠腹主动脉的MSCs，移植后早期细胞分布于肾皮质肾小球内；MSCs移植后早期可促进ARF恢复。

Objective To evaluate the efficacy of in vivo magnetic resonance imaging （MRI） of mesenchymal stem cells （MSCs） injected intravascularly in treatment of acute renal failure （ARF） , and to investigate the changes of renal function and pathology of ARF after MSC transplantation. Methods Rat MSCs were isolated and labeled with Fe2O3-PLL in vitro. Thirty SD rats underwent intramuscular injection of glycerol so as to establish ARF models and then randomly divided into 3 equal groups： Group I undergoing injection of labeled MSCs into ＇abdominal aorta via transcatheter, Group Ⅱ injected with unlabelled MSCs, and Group m injected with normal saline as controls. MRI of kidney was conducted before injection, and 0. 5 h, and 1, 2, and 5 days after injection. One and 2 days after the transplantation 3 rats from each group underwent MRI and extraction of blood samples from the abdominal aorta and then killed with their kidneys taken out, and 5 days after the rest rats were all killed after MRI with their kidneys taken out. Serum creatinine （Scr） and blood urea nitrogen （BUN） were examined so as to evaluate the renal function. Microscopy was conducted to observe the pathological changes. Prussian blue ＋ CD68 antibody staining was performed to identify the labeled MSCs. Results MRI showed decrease of signal intensity in renal cortex on the T2 ＊ -weighted MR images up to 5 days after transplantation. Histological analysis showed that most Prussian blue-positive cells were in the glomerular capillaries, corresponding to the areas where signal intensity decrease was observed by MRI. The Scr and BUN levels 2 and 5 days after the implantation of Group Ⅰ were both lower than those of the control group, and there were not significant differences in the Scr and BUN levels between Groups Ⅰ and Ⅱ. Renal tubular injury scoring showed that the renal tubular injury was significantly lighter than that of the control group. Conclusion 1.5-T MRI seems a good in vivo technique to monitor the magnetically labeled MSCs administered into the abdominal aorta of ARF animals, which are distributed in the glomerular capillaries in the early stage after transplantation. MSCs may promote the recovery of ARF.