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N-乙酰半胱氨酸可提高从严重脂肪变性供体肝组织中分离出的人肝细胞的活力。

N-acetylcysteine improves the viability of human hepatocytes isolated from severely steatotic donor liver tissue.

作者信息

Sagias Filippos G, Mitry Ragai R, Hughes Robin D, Lehec Sharon C, Patel Ameet G, Rela Mohamed, Mieli-Vergani Giorgina, Heaton Nigel D, Dhawan Anil

机构信息

Institute of Liver Studies, King's College London School of Medicine at King's College Hospital, London, UK.

出版信息

Cell Transplant. 2010;19(11):1487-92. doi: 10.3727/096368910X514620. Epub 2010 Jun 29.

Abstract

Hepatocyte transplantation is dependent on the availability of good quality human hepatocytes isolated from donor liver tissue. Hepatocytes obtained from livers rejected for transplantation on the grounds of steatosis are often of low viability and not suitable for clinical use. The aim of this study was to evaluate the effects of the antioxidant N-acetylcysteine (NAC) on the function of hepatocytes isolated from steatotic donor livers. Human hepatocytes were isolated from 10 severely steatotic (>60%) donor livers rejected for transplantation. The left lateral segment of the donor liver was dissected into two equal size pieces and randomized to NAC or control. NAC (5 mM) was added to the first perfusion buffer of the standard collagenase digestion technique. Cells from tissues perfused with NAC had a significantly higher mean viability (81.1 ± 1.7% vs. 66.0 ± 4.7%; p = 0.003) and cell attachment (1.08 ± 0.26 vs. 0.67 ± 0.18 OD units; p = 0.012). Addition of NAC during isolation of human hepatocytes from steatotic donor liver tissue significantly improved the outcome of cell isolation. Further studies are needed to investigate the mechanism(s) of this effect. Incorporation of NAC in the hepatocyte isolation protocol could increase the availability of hepatocytes for transplantation.

摘要

肝细胞移植依赖于从供体肝组织中分离出的高质量人肝细胞。因脂肪变性而被拒绝用于移植的肝脏所获得的肝细胞往往活力较低,不适合临床使用。本研究的目的是评估抗氧化剂N-乙酰半胱氨酸(NAC)对从脂肪变性供体肝脏分离出的肝细胞功能的影响。从10个因脂肪变性严重(>60%)而被拒绝用于移植的供体肝脏中分离出人肝细胞。将供体肝脏的左外侧叶切成两个大小相等的部分,并随机分为NAC组或对照组。在标准胶原酶消化技术的第一次灌注缓冲液中加入NAC(5 mM)。用NAC灌注的组织中的细胞平均活力显著更高(81.1±1.7%对66.0±4.7%;p = 0.003),细胞贴壁情况也更好(1.08±0.26对0.67±0.18 OD单位;p = 0.012)。在从脂肪变性供体肝脏组织中分离人肝细胞的过程中添加NAC可显著改善细胞分离效果。需要进一步研究来探讨这种作用的机制。在肝细胞分离方案中加入NAC可增加用于移植的肝细胞的可获得性。

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