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이두훈 대한간학회 2015 춘·추계 학술대회 (KASL) Vol.2015 No.2
More than nine types of bioartificial liver (BAL) systems have been clinically investigated, and their feasibility as a use of liver support system was partially verified. None of the BAL systems has received marketing approval that needs proof of its safety and survival gains. Due to the lack of functional activity of clinically studied BAL systems and difficulty of establishing manufacturing system for ready-to-use, additional research activities are stagnated. Rapid progressing stem cell technologies can lead to sufficient supply of functional human hepatocytes, and then, the bioartificial liver support system with human cells is widely used to treat patients with liver failure near future.
Hepatocyte Isolation, Culture, and Its Clinical Applications
이두훈,이광웅 한양대학교 의과대학 2014 Hanyang Medical Reviews Vol.34 No.4
Hepatocytes, parenchymal cells of the liver, are specially differentiated cells to perform most of the body metabolisms. Many clinicians are interested in utilizing hepatocytes as cell therapeutics. A great number of investigators have been harvesting hepatocytes using two-step portal vein perfusion method, in which Ca2+-free EDTA-containing buffer and Ca2+-enriched collagenase solution are pumped into liver in sequence. Among various attempts for long-term culture of hepatocytes, collagen gel sandwich configuration is recognized to be the most effective technique. In the biomedical field, hepatocytes have been used in three methods of applications. First is hepatocyte transplantation for the treatment of acute, chronic liver failure and metabolic diseases. Donated livers not suitable for organ transplantation are rare, which is the major human hepatocyte source. This shortage of human hepatocyte source is expected to be resolved by virtue of rapid progressing stem cell technologies. The second application is biological components of bioartificial liver (BAL) system for acute liver failure patients. Due to the lack of functional activity of clinically studied BAL systems and difficulty of establishing a manufacturing system for ready-to-use, additional research activities are stagnated. The third utilization of hepatocytes is in vitro drug screening studies such as drug metabolism, transport, biliary excretion, and toxicity tests. If cell therapeutic treatments using hepatocytes are clinically valuable to some types of liver diseases, the demand for liver transplantation would be significantly diminished.
이두훈,윤희훈,박정극 한국화학공학회 2004 Korean Chemical Engineering Research(HWAHAK KONGHA Vol.42 No.2
우리 인체의 장기 중 간(liver)은 생존에 그 어느 장기보다도 중요한 역할을 담당하는 장기로서 여러 가지 원인으로 인하여 갑자기 간의 기능이 상실된 환자에게는 간이식만이 유일한 대안이다. 간세포를 이용한 체외 순환형 간 보조 장치(생인공간, bioartificial liver)는 최근 유일하게 전격성 간부적 환자의 생존을 중대 효과가 검증되었고 간이식이나 환자 자신의 간 재생으로의 생명 연장 교량 역할을 효과적으로 수행할 수 있을 것으로 기대되고 있다. 본 논문에서는 생인공간의 개념과 임상시험 중인 대표적인 생인공간 시스템 현황에 대해서 공학적 관점 위주로 소개하고 향후 이 분야에 대한 연구전망에 대하여 서술하였다. The liver is mutifunctional vital organ for healthy survival and orthotopic liver transplantation is the only definitive therapy for patients with acute or fulminant hepatic failure(FHF) so far. Bioartificial liver, a hepatocyte-based extracorporeal liver support system, enhanced the survival rates of patients with FHF and expected to act as a bridge to provide the extension of survival time until a donor organ becomes available for transplantation or their own liver can be regenerated. In this paper, we introduce concepts of bioartificial liver and review representative bioartifical liver systems in clinical trials with engineering issue. Finally we describe future perspectives of bioartificial liver.