Pascual-Miguelañez Isabel, Salinas-Gomez Javier, Fernandez-Luengas David, Villar-Zarra Karen, Clemente Luz Vega, Garcia-Arranz Mariano, Olmo Damian Garcia
1Hospital Universitario Infanta Sofía, Spain.
J Invest Surg. 2015 Apr;28(2):120-6. doi: 10.3109/08941939.2014.987407. Epub 2014 Dec 17.
The definitive treatment for liver failure is, currently, liver transplantation. Research into other possible treatments, focused on achieving regeneration of the liver parenchyma, have led to the development of methods to generate hepatocytes from stem cells. In our study, we transplant allogenic adipose-derived stem cells (ASCs), not previously differentiated to hepatocytes, to treat acute liver failure induced by intraperitoneal administration of carbon tetrachloride (CCl4) in a Sprague-Dawley rat model.
The ASCs were delivered via the tail vein, having previously been labeled with PKH26, a fluorescent membrane marker. Two control groups were established, Group 1(n = 15) consisting of olive oil (5 mL/kg) and Group 2(n = 15): 1 × 10(6) PKH26-labeled ASCs. Further, two study groups, Group 3(n = 30): CCl4 dissolved in olive oil and Group 4(n = 30): CCl4 dissolved in olive oil and 1 × 10(6) PKH26-labeled ASCs completed the experimental design.
Blood samples were analyzed, finding AST and ALT levels significantly higher in treatment over control groups at 24 and 48 hours. The mortality rates were statistically different between control groups and Group 3 (Group 1-3 p = .04, Group 2-3 p = .04) and between Groups 3 and 4 (p = .02). Examining the liver parenchyma, a significantly higher number of ASCs were observed in Group 4 than in Group 2 at all time points (p = .00).
The intravenous injection of allogenic ASCs in this model of CCl4-induced liver failure reduced the mortality in treated animals. ASCs injected in the rat tail vein were found in the liver in animals with induced acute liver failure.
目前,肝衰竭的最终治疗方法是肝移植。针对其他可能治疗方法的研究聚焦于实现肝实质再生,这促使了从干细胞生成肝细胞方法的发展。在我们的研究中,我们将未预先分化为肝细胞的同种异体脂肪来源干细胞(ASC)移植到Sprague-Dawley大鼠模型中,以治疗腹腔注射四氯化碳(CCl4)诱导的急性肝衰竭。
ASC通过尾静脉注射,此前已用荧光膜标记物PKH26进行标记。设立两个对照组,第1组(n = 15)由橄榄油(5 mL/kg)组成,第2组(n = 15):1×10(6)个PKH26标记的ASC。此外,两个研究组,第3组(n = 30):溶解于橄榄油中的CCl4,第4组(n = 30):溶解于橄榄油中的CCl4和1×10(6)个PKH26标记的ASC,完成了实验设计。
对血液样本进行分析,发现治疗组在24小时和48小时时AST和ALT水平显著高于对照组。对照组与第3组之间(第1组 - 第3组p = 0.04,第2组 - 第3组p = 0.04)以及第3组和第4组之间(p = 0.02)的死亡率在统计学上存在差异。检查肝实质,在所有时间点,第4组中观察到的ASC数量均显著高于第2组(p = 0.00)。
在该CCl4诱导的肝衰竭模型中,静脉注射同种异体ASC可降低治疗动物的死亡率。在诱导急性肝衰竭的动物肝脏中发现了经大鼠尾静脉注射的ASC。