Hybrid artificial liver using hepatocyte organoid culture

被引:76
作者
Funatsu, K
Ijima, H
Nakazawa, K
Yamashita, Y
Shimada, M
Sugimachi, K
机构
[1] Kyushu Univ, Fac Engn, Dept Chem Engn, Higashi Ku, Fukuoka 8128581, Japan
[2] Kyushu Univ, Fac Med Sci, Dept Surg & Sci, Higashi Ku, Fukuoka 8128581, Japan
关键词
hybrid artificial liver support system; polyurethane foam; spheroid; hollow fiber; hepatocyte organoid; preclinical experiment;
D O I
10.1046/j.1525-1594.2001.025003194.x
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
We developed 2 types of hybrid artificial liver modules using hepatocyte organoid culture. One was a polyurethane foam (PUF)/hepatocyte spheroid packed-bed module. Hepatocytes spontaneously formed spheroids in the PUF pores, and they maintained liver-specific functions well for at least 2 weeks in vitro. As a preclinical experiment, a hybrid artificial liver with 200 g porcine hepatocytes was applied to a pig (25 kg) with liver failure and showed that the hybrid artificial liver was effective in support of Liver functions and stabilization of general conditions. We established a new technique of hepatocyte organoid formation using centrifugal force. A hepatocyte organoid formed by centrifugation in hollow fibers maintained functions for more than 4 months in vitro. We developed a new sinusoid-like structure module having hollow fibers arranged by spacers in a micro-regular arrangement. Inoculated hepatocytes in the extra-fiber space of the module formed the organoid by centrifugation, and they maintained the functions for at least 1 month in vitro. The results indicated that this module seems to be promising as a hybrid artificial liver.
引用
收藏
页码:194 / 200
页数:7
相关论文
共 44 条
[1]   HEMODIABSORPTION IN TREATMENT OF ACUTE HEPATIC-FAILURE AND CHRONIC CIRRHOSIS WITH ASCITES [J].
ASH, SR .
ARTIFICIAL ORGANS, 1994, 18 (05) :355-362
[2]   A NOVEL BIOREACTOR DESIGN FOR IN-VITRO RECONSTRUCTION OF IN-VIVO LIVER CHARACTERISTICS [J].
BADER, A ;
KNOP, E ;
BOKER, K ;
FRUHAUF, N ;
SCHUTTLER, W ;
OLDHAFER, K ;
BURKHARD, R ;
PICHLMAYR, R ;
SEWING, KF .
ARTIFICIAL ORGANS, 1995, 19 (04) :368-374
[3]   Artificial liver support: State of the art [J].
Dixit, V ;
Gitnick, G .
SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY, 1996, 31 :101-114
[4]  
Flendrig LM, 1997, ARTIF ORGANS, V21, P1177
[5]   Cell-based therapy of acute liver failure: The extracorporeal bioartificial liver [J].
Fremond, B ;
Joly, A ;
Desille, M ;
Desjardins, JF ;
Campion, JP ;
Clement, B .
CELL BIOLOGY AND TOXICOLOGY, 1996, 12 (4-6) :325-329
[6]   Intensive promotion of spheroid formation by soluble factors in a hepatocyte-conditioned medium [J].
Fujii, Y ;
Nakazawa, K ;
Funatsu, K .
JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION, 2000, 11 (07) :731-745
[7]   IMPROVED HEPATOCYTE IN-VITRO MAINTENANCE IN A CULTURE MODEL WITH WOVEN MULTICOMPARTMENT CAPILLARY SYSTEMS - ELECTRON-MICROSCOPY STUDIES [J].
GERLACH, JC ;
SCHNOY, N ;
ENCKE, J ;
SMITH, MD ;
MULLER, C ;
NEUHAUS, P .
HEPATOLOGY, 1995, 22 (02) :546-552
[8]   Evaluation of a hybrid artificial liver using a polyurethane foam packed-bed culture system in dogs [J].
Gion, T ;
Shimada, M ;
Shirabe, K ;
Nakazawa, K ;
Ijima, H ;
Matsushita, T ;
Funatsu, K ;
Sugimachi, K .
JOURNAL OF SURGICAL RESEARCH, 1999, 82 (02) :131-136
[9]   Modulation of immunologic reactions between cultured porcine hepatocytes and human sera [J].
Hasegawa, H ;
Shimada, M ;
Gion, T ;
Ijima, H ;
Nakazawa, K ;
Funatsu, K ;
Sugimachi, K .
ASAIO JOURNAL, 1999, 45 (05) :392-396
[10]   Development of a bioartificial liver employing xenogeneic hepatocytes [J].
Hu, WS ;
Friend, JR ;
Wu, FJ ;
Sielaff, T ;
Peshwa, MV ;
Lazar, A ;
Nyberg, SL ;
Remmel, RP ;
Cerra, FB .
CYTOTECHNOLOGY, 1997, 23 (1-3) :29-38