Department of Biochemistry and Molecular Biology II, School of Pharmacy, University of Granada, Campus de Cartuja, 18071 Granada, Spain.
Cell Transplant. 2009;18(10):1069-79. doi: 10.3727/096368909X12483162197088. Epub 2009 Jun 22.
Our research group investigates whether human mononuclear cells isolated from umbilical cord blood (HUCBM cells) might be valuable in hepatic regenerative medicine. We recently demonstrated that HUCBM cell transplantation improves histological alterations and function of the liver in rats with acute liver damage induced by D-galactosamine. In the present study, HUCBM cells were transplanted into rats with thioacetamide (TAA)-induced liver cirrhosis, an experimental model that generates an intense fibrosis and mimics the histological and biochemical alterations found in the human disease. HUCBM transplantation had no effect on hepatic histology of cirrhotic animals. In contrast, analysis of plasma albumin and total bilirubin, liver damage markers, revealed a harmful effect of HUCBM cell transplantation in our experimental model of liver cirrhosis. Significantly higher plasma urea concentrations, marker of renal function, were observed in the cirrhotic and control rats intraportally injected with HUCBM cells than in those not receiving this therapy. Histological study revealed tubular and glomerular lesions in kidneys of cirrhotic animals transplanted with HUCBM cells. The glomeruli appeared ischemic, and the tubules showed a severe involvement that included peripheral asymmetric vacuolization and disappearance of the tubular lumen. Taken together, the histological and biochemical data suggest that the cirrhotic rats subjected to HUCBM cell therapy developed a hepatorenal syndrome.
我们的研究小组研究了从脐血中分离出的人类单核细胞(HUCBM 细胞)是否可用于肝脏再生医学。我们最近证明,HUCBM 细胞移植可改善 D-半乳糖胺诱导的急性肝损伤大鼠的肝脏组织学改变和功能。在本研究中,将 HUCBM 细胞移植到硫代乙酰胺(TAA)诱导的肝硬化大鼠中,该实验模型可产生强烈的纤维化,并模拟人类疾病中的组织学和生化改变。HUCBM 移植对肝硬化动物的肝组织学没有影响。相比之下,对血浆白蛋白和总胆红素(肝功能损伤标志物)的分析表明,HUCBM 细胞移植对我们的肝硬化实验模型具有有害作用。与未接受该治疗的大鼠相比,经门静脉内注射 HUCBM 细胞的肝硬化和对照组大鼠的血浆尿素浓度(肾功能标志物)显著升高。组织学研究显示,接受 HUCBM 细胞移植的肝硬化动物的肾脏出现管状和肾小球病变。肾小球呈缺血性,肾小管严重受累,包括周边非对称空泡化和管腔消失。综上所述,组织学和生化数据表明,接受 HUCBM 细胞治疗的肝硬化大鼠发生了肝肾综合征。