Department of Gastroenterology, The First Hospital, Jilin University, Changchun, 130021, China.
J Hepatobiliary Pancreat Sci. 2011 May;18(3):397-405. doi: 10.1007/s00534-010-0343-8.
BACKGROUND/PURPOSE: Bone marrow mononuclear cell (BMMC) transplantation has been shown to facilitate tissue and organ regeneration and repair. BMMC transplantation may be a potential therapy for acute liver failure, and its effect might be further improved. Hepatocyte growth factor (HGF) plays an important role in liver cell development, and may ameliorate hepatic fibrosis or cirrhosis in animal models. We therefore explored a potential synergistic effect of the co-application of HGF and BMMCs in liver regeneration following carbon tetrachloride (CCl(4))-induced acute hepatic injury.
We established a murine acute liver failure model induced by CCl(4) administration, and studied the effect of BMMC transplantation in combination with HGF. We used 4 groups of animals, one group was transfused with PKH26-labeled BMMCs (5 × 10(6)) and HGF [50 ng/(kg days) × 7 days] (BMMCs + HGF group), one group received BMMCs only, one group received HGF only, and one group received saline solution (0.9% NaCl) alone. The effects were examined by biochemical measurements of liver enzymes and quantitative image analysis for PKH26 labeling, and by determining proliferating cell nuclear antigen (PCNA) and albumin expression 4 weeks after the BMMC transplantation.
PKH26-labeled BMMCs were detected in transplanted mouse livers, most of which expressed PCNA. PCNA and albumin expressions were increased significantly in the BMMCs + HGF group compared with the expressions of these parameters in the other 3 groups. Liver function, reflected by serum aminotransferase activity, was also improved in the BMMCs + HGF group relative to that in the other groups.
Data from the present study appear to suggest that BMMC transplantation combined with HGF administration exhibits a synergistic beneficial effect on improving both functional and histological liver recovery in a mouse model of acute liver failure.
背景/目的：骨髓单个核细胞（BMMC）移植已被证明可促进组织和器官的再生和修复。BMMC 移植可能是急性肝衰竭的一种潜在治疗方法，并且其效果可能会进一步提高。肝细胞生长因子（HGF）在肝细胞发育中起重要作用，并可能改善动物模型中的肝纤维化或肝硬化。因此，我们探索了在四氯化碳（CCl 4 ）诱导的急性肝损伤后，HGF 与 BMMC 联合应用对肝脏再生的潜在协同作用。
我们建立了四氯化碳诱导的急性肝衰竭小鼠模型，并研究了 BMMC 移植与 HGF 联合应用的效果。我们使用 4 组动物，一组输注 PKH26 标记的 BMMC（5×10 6 ）和 HGF[50ng/（kg·天）×7 天]（BMMC+HGF 组），一组仅接受 BMMC，一组仅接受 HGF，一组仅接受生理盐水（0.9%NaCl）。通过检测肝酶的生化指标和 PKH26 标记的定量图像分析，以及检测 4 周后增殖细胞核抗原（PCNA）和白蛋白的表达，来评估效果。
在移植的小鼠肝脏中检测到 PKH26 标记的 BMMC，其中大多数表达 PCNA。与其他 3 组相比，BMMC+HGF 组的 PCNA 和白蛋白表达显著增加。BMMC+HGF 组的肝功能，反映在血清转氨酶活性上，也比其他组有所改善。
本研究的数据似乎表明，BMMC 移植联合 HGF 给药在改善急性肝衰竭小鼠模型的肝功能和组织学恢复方面具有协同的有益作用。
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