Development of cell therapy using autologous bone marrow cells for liver cirrhosis

Development of cell therapy using autologous bone marrow cells for liver cirrhosis
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DOI:
10.1007/s00795-005-0298-z
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发表时间:
2005-12-01
影响因子:
1.8
通讯作者:
Okita, Kiwamu
Okita, Kiwamu
中科院分区:
医学4区
文献类型:
--
作者:
Sakaida, Isao;Terai, Shuji;Okita, Kiwamu

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一名接受男性供者骨髓细胞移植的女性的尸检证实了骨髓的可塑性。为了建立利用自体骨髓细胞治疗肝功能衰竭患者的新的临床细胞疗法,我们开发了一种新的体内模型,称为绿色荧光蛋白(GFP)/四氯化碳(CCl4)模型。利用GFP/CCl4模型,我们发现在四氯化碳诱导的持续性肝损伤下,移植的Liv8阴性细胞能够有效地重新植入肝硬变组织并分化为产生白蛋白的肝细胞。此外,骨髓细胞移植改善了肝硬变小鼠的肝功能和肝纤维化,增强了基质金属蛋白酶(MMPs)的表达,尤其是MMP9的活性,从而提高了存活率。GFP/CCl4模型的结果表明,使用自体骨髓细胞的细胞疗法有可能成为治疗肝功能衰竭患者的有效方法。对GFP/CCl4模型的研究结果进行了总结。
The plasticity of bone marrow has been confirmed by the autopsy of a female recipient of bone marrow cell transplantation from a male donor. To establish new clinical cell therapies using autologous bone marrow cells for patients with liver failure, we developed a new in vivo model named the green fluorescent protein (GFP)/carbon tetrachloride (CCl4) model. Using the GFP/CCl4 model, we found that transplanted Liv8-negative cells efficiently repopulated into cirrhotic liver tissue and differentiated into albumin-producing hepatocytes under persistent liver damage induced by carbon tetrachloride. Moreover, bone marrow cell transplantation into mice with liver cirrhosis improved liver function and liver fibrosis with the strong expression of matrix metalloproteinases (MMPs), especially MMP-9 activity, resulting in an improved survival rate. Results from the GFP/CCl4 model showed that cell therapy using autologous bone marrow cells has the potential to become an effective treatment for patients with liver failure. A summary of findings from the GFP/CCl4 model is described.