臨牀消化器内科 Vol.23 No.13(3-4)


特集名 急性肝不全と再生医療
題名 肝不全と再生医療 (4) 致死的肝性脳症改善のための体外循環型バイオ人工肝臓の開発
発刊年月 2008年 12月
著者 松浦 知和 東京慈恵会医科大学臨床検査医学講座
著者 岩城 隆昌 東京慈恵会医科大学実験動物研究施設
著者 木村 直史 東京慈恵会医科大学薬理学講座
【 要旨 】 体外循環型バイオ人工肝臓は,欧米の多臨床施設でのコホート研究では,肝性脳症の改善に有用であることが証明されている.しかし,「なぜバイオ人工肝臓が脳症を改善するのか?」という根本的な問題が解決されていない.本稿では,ラジアルフロー型バイオリアクターと高機能ヒト肝癌細胞株で構築した体外循環型バイオ人工肝臓を作製し,ブタ急性肝不全モデルに適用したところ,脳症の改善によって救命できたので紹介する.この実験結果から,バイオ人工肝臓によって肝性脳症惹起物質が除去されたと推察されるが,バイオ人工肝臓開発研究を通じて未知の肝性脳症惹起物質を明らかにできれば,より安価で簡易な致死的肝性脳症を回避するための体外循環システムを構築できる.
Theme Acute Liver Failure and Regenerative Medicine of the Liver
Title Extracorporeal Bioartificial Liver Support System for Treatment of Fatal Hepatic Encephalopathy
Author Tomokazu Matsuura Department of Laboratory Medicine, The Jikei University School of Medicine
Author Takamasa Iwaki Laboratory Animal Facilities, The Jikei University School of Medicine
Author Naofumi Kimura Department of Pharmacology, The Jikei University School of Medicine
[ Summary ] An extracorporeal bioartificial liver consists of liver cells and abioreactor. Recently, developments in bioreactor and normal cells research, to produce bioartificial livers have advanced rapidly and reached the level of practical use. In addition, from the results of case control studies and cohort studies concerning clinical applications for artificial livers, artificial livers have been determined to be useful for improving treatments for hepaticenc ephalopathy. We aimed to develop an extracorporeal bioartificial liver (BAL) that could prevent death from hepaticenc ephalopathy in case of acute hepatic insufficiency. A functional human hepatocellular carcinoma cell line (FLC-4) was cultured in a radial-flow bioreactor (RFB). The functionality of the BAL was tested in mini-pigs with acute hepatic failure, induced by a-amanitin and lipopolysaccaride. When the BAL system was connected to cultured FLC-4 in three pigs with hepatic dysfunction, all demonstrated electroencephalographic (EEG) improvement and survived. BAL therapy can prevent irreversible brain damage from hepatic encephalopathy in experimental acute hepatic failure. It is necessary to examine how we evaluate bioartificial liver support as an adjuvant therapy in over all hepatic dysfunction treatment.
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