Yocum Gene T, Wilson Lindsey B, Ashari Parwana, Jordan E Kay, Frank Joseph A, Arbab Ali S
Experimental Neuroimaging Section, Laboratory of Diagnostic Radiology Research, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA.
Radiology. 2005 May;235(2):547-52. doi: 10.1148/radiol.2352040383.
To determine whether ferumoxides-poly-l-lysine (PLL) complex-labeled mesenchymal stem cells (MSCs) or ferumoxides-PLL complex alone alters hematologic, blood chemistry, renal function, and/or liver function measurements after being intravenously infused into rats.
Twenty-five rats (group 1) received intravenous injections of labeled MSCs, and 25 additional rats (group 2) received intravenous injections of ferumoxides-PLL complex only. Complete blood counts, liver and renal function test results, and serum electrolyte and iron concentrations were measured for 42 days after the injections and compared with those measured in five control rats (group 3). To determine the duration of labeled MSCs in the circulation, venous blood was serially drawn from five additional rats (group 4) that were injected with labeled MSCs. Analyses of variance (ANOVA) followed by Fisher protected least significant difference post hoc tests were used to statistically analyze results. P < .05 was considered to indicate significance in all analyses.
Administration of neither labeled MSCs nor ferumoxides-PLL complex had a significant effect on hematologic or blood chemistry indicators of organ function. Of the parameters measured, only hemoglobin concentration and mean corpuscular volume (MCV) in the rats injected with labeled MSCs, as well as MCV and hemoglobin, alkaline phosphatase, aspartate aminotransferase, and direct bilirubin concentrations in the rats injected with ferumoxides-PLL complex, varied significantly during the 42-day postinjection period (P < .05, ANOVA). No other measurements, including serum electrolyte and iron concentrations, changed significantly during the test period (P > .05). Furthermore, injected labeled MSCs had cleared from the peripheral circulation by 15 minutes after injection.
Results indicate that infusing cells that are magnetically labeled with ferumoxides-PLL complex into rats does not alter biochemical or hematologic measures of organ function in a clinically relevant or preclusive manner.
确定静脉注射到大鼠体内后,超顺磁性氧化铁-聚-L-赖氨酸(PLL)复合物标记的间充质干细胞(MSCs)或单独的超顺磁性氧化铁-PLL复合物是否会改变血液学、血液化学、肾功能和/或肝功能指标。
25只大鼠(第1组)接受静脉注射标记的MSCs,另外25只大鼠(第2组)仅接受静脉注射超顺磁性氧化铁-PLL复合物。注射后42天测量全血细胞计数、肝肾功能测试结果以及血清电解质和铁浓度,并与5只对照大鼠(第3组)的测量结果进行比较。为了确定标记的MSCs在循环中的持续时间,从另外5只注射了标记MSCs的大鼠(第4组)中连续采集静脉血。采用方差分析(ANOVA),随后进行Fisher保护最小显著差异事后检验对结果进行统计学分析。所有分析中,P < 0.05被认为具有统计学意义。
注射标记的MSCs或超顺磁性氧化铁-PLL复合物均未对器官功能的血液学或血液化学指标产生显著影响。在测量的参数中,仅注射标记MSCs的大鼠的血红蛋白浓度和平均红细胞体积(MCV),以及注射超顺磁性氧化铁-PLL复合物的大鼠的MCV、血红蛋白、碱性磷酸酶、天冬氨酸转氨酶和直接胆红素浓度在注射后42天内有显著变化(P < 0.05,ANOVA)。在测试期间,包括血清电解质和铁浓度在内的其他测量结果均无显著变化(P > 0.05)。此外,注射的标记MSCs在注射后15分钟已从外周循环中清除。
结果表明,将用超顺磁性氧化铁-PLL复合物进行磁性标记的细胞注入大鼠体内,不会以临床相关或排除性的方式改变器官功能的生化或血液学指标。