Attaran Masoumeh, Schneider Andrea, Grote Christiane, Zwiens Caroline, Flemming Peer, Gratz Klaus F, Jochheim Andrea, Bahr Matthias J, Manns Michael P, Ott Michael
Department of Gastroenterology, Hepatology and Endocrinology, Center of Internal Medicine, Hannover Medical School, Carl-Neubergstr. 1, 30625 Hannover, Germany.
J Hepatol. 2004 Nov;41(5):837-44. doi: 10.1016/j.jhep.2004.07.014.
BACKGROUND/AIMS: Hepatocyte transplantation has the potential to become an alternative to organ transplantation for the treatment of hereditary liver disease. Currently used hepatocyte transplantation techniques are often not sufficient for phenotypic correction. In a pre-clinical model we investigated the effect of regional transient ischemia reperfusion injury and repeated infusions of allogeneic hepatocytes on LDL cholesterol levels in LDL receptor deficient hyperlipidemic Watanabe rabbits.
A catheter was surgically inserted into the inferior mesenteric vein. Blood supply to the right liver lobe was transiently interrupted. Nine infusions of 2.5x10(7) adult allogeneic hepatocytes from white New Zealand rabbits were applied over a period of 2 months.
Compared to pretreatment levels LDL cholesterol decreased significantly in Watanabe rabbits with transient ischemia reperfusion injury and repeated hepatocyte transplantation (-42+/-3%). Repeated hepatocyte transplantation without transient ischemia reperfusion injury decreased LDL cholesterol levels only moderately (-11+/-4%). LDL receptor messenger RNA and proteins were detected in hepatocyte transplanted liver but not in the liver of sham treated animals.
Our data indicate that transient ischemia reperfusion injury of the recipient liver is safe and significantly improves the therapeutic efficacy of allogeneic hepatocyte transplantation in hyperlipidemic rabbits with congenital LDL receptor deficiency.
背景/目的：肝细胞移植有潜力成为治疗遗传性肝病的器官移植替代方法。目前使用的肝细胞移植技术通常不足以实现表型纠正。在一个临床前模型中，我们研究了局部短暂缺血再灌注损伤和重复输注同种异体肝细胞对低密度脂蛋白受体缺陷型高脂血症渡边兔低密度脂蛋白胆固醇水平的影响。
通过手术将导管插入肠系膜下静脉。右肝叶的血液供应被短暂中断。在2个月的时间内，分9次输注来自白色新西兰兔的2.5×10(7)个成年同种异体肝细胞。
与预处理水平相比，经历短暂缺血再灌注损伤并接受重复肝细胞移植的渡边兔的低密度脂蛋白胆固醇显著降低（-42±3%）。未经历短暂缺血再灌注损伤的重复肝细胞移植仅使低密度脂蛋白胆固醇水平适度降低（-11±4%）。在接受肝细胞移植的肝脏中检测到低密度脂蛋白受体信使核糖核酸和蛋白质，但在假手术处理动物的肝脏中未检测到。
我们的数据表明，受体肝脏的短暂缺血再灌注损伤是安全的，并且显著提高了先天性低密度脂蛋白受体缺陷的高脂血症兔同种异体肝细胞移植的治疗效果。
