Prevention of acute liver failure in rats with reversibly immortalized human hepatocytes
Prevention of acute liver failure in rats with reversibly immortalized human hepatocytes
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DOI：
10.1126/science.287.5456.1258
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发表时间：
2000-02-18
期刊：
影响因子：
56.9
通讯作者：
Leboulch, P
中科院分区：
文献类型：
--
作者：
Kobayashi, N;Fujiwara, T;Leboulch, P
由于合适的器官严重短缺，每年都有许多晚期肝病患者在肝移植之前死亡。已提出移植离体肝细胞用于等待肝移植或其肝病自发逆转的患者的临时代谢支持。这种形式的治疗的主要限制是目前无法分离足够数量的可移植肝细胞。一个高度分化的细胞系，NKNT-3，产生的逆转录病毒转移在正常的原代成人肝细胞的永生化基因，可以随后和完全切除的Cre/Lox位点特异性重组。当移植到短暂免疫抑制下的大鼠脾脏中时，可逆永生化的NKNT-3细胞在90%肝切除术诱导的急性肝衰竭期间提供了挽救生命的代谢支持。
Because of a critical shortage in suitable organs, many patients with terminal liver disease die each year before liver transplantation can be performed. Transplantation of isolated hepatocytes has been proposed for the temporary metabolic support of patients awaiting liver transplantation or spontaneous reversion of their liver disease. A major limitation of this form of therapy is the present inability to isolate an adequate number of transplantable hepatocytes. A highly differentiated cell line, NKNT-3, was generated by retroviral transfer in normal primary adult human hepatocytes of an immortalizing gene that can be subsequently and completely excised by Cre/Lox site-specific recombination. When transplanted into the spleen of rats under transient immunosuppression, reversibly immortalized NKNT-3 cells provided life-saving metabolic support during acute liver failure induced by 90% hepatectomy.