Stem cell therapy for liver disease: Parameters governing the success of using bone marrow mesenchymal stem cells
Stem cell therapy for liver disease: Parameters governing the success of using bone marrow mesenchymal stem cells
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DOI：
10.1053/j.gastro.2008.03.015
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发表时间：
2008-06-01
期刊：
影响因子：
29.4
通讯作者：
Lee, Oscar K.
中科院分区：
文献类型：
--
作者：
Kuo, Tom K.;Hung, Shun-Pei;Lee, Oscar K.
背景与目的：肝移植是各种终末期肝病的主要治疗方法，但由于缺乏供体器官以及与排斥和免疫抑制相关的并发症而受到阻碍。越来越多的证据表明骨髓是肝祖细胞的可移植来源。我们之前报道过，多能骨髓间充质干细胞在特定条件下分化为功能性肝细胞样细胞，诱导频率几乎为 100%，这表明其具有临床应用的潜力。本研究的目的是批判性地分析控制基于骨髓间充质干细胞的肝病治疗成功的各种参数。方法：采用四氯化碳灌胃法诱导非肥胖糖尿病严重联合免疫缺陷小鼠致死性暴发性肝衰竭。然后将间充质干细胞来源的肝细胞和间充质干细胞以不同剂量进行脾内或静脉内移植。结果：间充质干细胞来源的肝细胞和间充质干细胞通过脾内或静脉途径移植，移植到受体肝脏中，分化为功能性肝细胞，并挽救了肝衰竭。静脉移植比脾内移植在挽救肝衰竭方面更有效。此外，间充质干细胞在体外对活性氧具有更强的抵抗力，减少受体小鼠的氧化应激，并加速肝损伤后肝细胞的再生，这表明旁分泌作用可能发挥作用。结论：骨髓间充质干细胞可以有效挽救实验性肝衰竭，并有助于肝脏再生，为肝病的器官移植治疗提供潜在的替代疗法。
Background & Aims: Liver transplantation is the primary treatment for various end-stage hepatic diseases but is hindered by the lack of donor organs and by complications associated with rejection and immuno suppression. There is increasing evidence to suggest the bone marrow is a transplantable source of hepatic progenitors. We previously reported that multipotent bone marrow-derived mesenchymal stem cells differentiate into functional hepatocyte-like cells with almost 100% induction frequency under defined conditions, suggesting the potential for clinical applications. The aim of this study was to critically analyze the various parameters governing the success of bone marrow-derived mesenchymal stem cell-based therapy for treatment of liver diseases. Methods: Lethal fulminant hepatic failure in nonobese diabetic severe combined immunodeficient mice was induced by carbon tetrachloride gavage. Mesenchymal stem cell-derived hepatocytes and mesenchymal stem cells were then intrasplenically or intravenously transplanted at different doses. Results: Both mesenchymal stem cell-derived hepatocytes and mesenchymal stem cells, transplanted by either intrasplenic or intravenous route, engrafted recipient liver, differentiated into functional hepatocytes, and rescued liver failure. Intravenous transplantation was more effective in rescuing liver failure than intrasplenic transplantation. Moreover, mesenchymal stem cells were more resistant to reactive oxygen species in vitro, reduced oxidative stress in recipient mice, and accelerated repopulation of hepatocytes after liver damage, suggesting a possible role for paracrine effects. Conclusions: Bone marrow-derived mesenchymal stem cells can effectively rescue experimental liver failure and contribute to liver regeneration and offer a potentially alternative therapy to organ transplantation for treatment of liver diseases.