Sakaida Isao
Department of Gastroenterology and Hepatology, Yamaguchi University, Graduate School of Medicine, Ube, Yamaguchi Prefecture, Japan.
J Gastroenterol Hepatol. 2008 Sep;23(9):1349-53. doi: 10.1111/j.1440-1746.2008.05381.x. Epub 2008 Apr 19.
The plasticity of bone marrow cells (BMC) has been confirmed by autopsy results of female recipients of BMC from male donors. To establish new clinical therapies for patients with liver cirrhosis using autologous BMC, we developed a new in vivo murine model using green fluorescent protein (GFP) and repeated carbon tetrachloride (CCl(4)) injection. We found that BMC infused through the tail vein, efficiently repopulated cirrhotic liver tissue and, under the influence of persistent liver damage induced by carbon tetrachloride, differentiated into albumin-producing hepatocytes. Moreover, such BMC infusions into mice with cirrhosis improved liver function and reduced mortality. The latter observation correlated with the strong expression of matrix metalloproteinases (MMP), particularly MMP-9, and reduced hepatic fibrosis. The results from the 'GFP/CCl(4) model' showed that cell therapy using autologous BMC has the potential to become an effective treatment for patients with liver failure due to advanced liver cirrhosis. This review summarizes previous findings plus these recent experimental results, as well as recent clinical trials of BMC transfusion into patients with end-stage chronic liver disease.
来自男性供体的骨髓细胞(BMC)移植给女性受者的尸检结果证实了骨髓细胞的可塑性。为了利用自体骨髓细胞为肝硬化患者开发新的临床治疗方法,我们利用绿色荧光蛋白(GFP)和反复注射四氯化碳(CCl₄)建立了一种新的体内小鼠模型。我们发现,通过尾静脉注入的骨髓细胞有效地重新填充了肝硬化肝组织,并在四氯化碳诱导的持续性肝损伤的影响下,分化为产生白蛋白的肝细胞。此外,将这种骨髓细胞注入肝硬化小鼠可改善肝功能并降低死亡率。后一观察结果与基质金属蛋白酶(MMP),特别是MMP-9的强烈表达以及肝纤维化减轻相关。“GFP/CCl₄模型”的结果表明,使用自体骨髓细胞进行细胞治疗有可能成为晚期肝硬化所致肝衰竭患者的有效治疗方法。本综述总结了先前的研究结果以及这些最新的实验结果,以及向终末期慢性肝病患者输注骨髓细胞的近期临床试验情况。