Proliferation rates of HepG2 cells encapsulated in alginate are increased in a microgravity environment compared with static cultures

被引:43
作者
Coward, SM
Selden, C
Mantalaris, A
Hodgson, HJF
机构
[1] UCL Royal Free & Univ Coll Med Sch, Ctr Hepatol, London NW3 2PF, England
[2] Univ London Imperial Coll Sci Technol & Med, London, England
关键词
liver; artificial; bioreactors; cell line; tumor; hepatocytes; rotating vessel;
D O I
10.1111/j.1525-1594.2005.29026.x
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
This study investigates the effect of rotary culture compared with static culture on the proliferation, cell viability, synthetic function and detoxificatory capacity of HepG2 cells encapsulated in 1% alginate. Cell viability and alginate bead morphology were maintained in the rotary culture system at day 10, while cell number showed a 4.5-fold increase compared with static culture. Protein production was increased in rotary cultures with a 4.1-fold increase in total albumin and a 4.4-fold increase in alpha1 antitrypsin levels in rotary compared with static culture at day 10. CYP4501A1/2 activity was maintained between the two culture systems. In conclusion, rotary culture increases proliferation rates leading to improved bead packing and a concomitant increase in total protein synthesis, along with maintenance of detoxificatory capacity. This allows a greater level of hepatic function to be expressed in a given volume, offering clear advantages for the design of liver support systems.
引用
收藏
页码:152 / 158
页数:7
相关论文
共 18 条
[1]   A MICROASSAY FOR MEASURING CYTOCHROME-P450IA1 AND CYTOCHROME-P450IIB1 ACTIVITIES IN INTACT HUMAN AND RAT HEPATOCYTES CULTURED ON 96-WELL PLATES [J].
DONATO, MT ;
GOMEZLECHON, MJ ;
CASTELL, JV .
ANALYTICAL BIOCHEMISTRY, 1993, 213 (01) :29-33
[2]   Bioflavonoids: selective substrates and inhibitors for cytochrome P450CYP1A and CYP1B1 [J].
Doostdar, H ;
Burke, MD ;
Mayer, RT .
TOXICOLOGY, 2000, 144 (1-3) :31-38
[3]   Pilot-controlled trial of the extracorporeal liver assist device in acute liver failure [J].
Ellis, AJ ;
Hughes, RD ;
Wendon, JA ;
Dunne, J ;
Langley, PG ;
Kelly, JH ;
Gislason, GT ;
Sussman, NL ;
Williams, R .
HEPATOLOGY, 1996, 24 (06) :1446-1451
[4]   Cytochrome P450 regulation by hepatocyte nuclear factor 4 in human hepatocytes:: A study using adenovirus-mediated antisense targeting [J].
Jover, R ;
Bort, R ;
Gómez-Lechón, MJ ;
Castell, JV .
HEPATOLOGY, 2001, 33 (03) :668-675
[5]   Human hepatocyte cell lines proliferating as cohesive spheroid colonies in alginate markedly upregulate both synthetic and detoxificatory liver function [J].
Khalil, M ;
Shariat-Panahi, A ;
Tootle, R ;
Ryder, T ;
McCloskey, P ;
Roberts, E ;
Hodgson, H ;
Selden, C .
JOURNAL OF HEPATOLOGY, 2001, 34 (01) :68-77
[6]  
Khaoustov VI, 1999, IN VITRO CELL DEV-AN, V35, P501
[7]  
KOCAREK TA, 1993, IN VITRO CELL DEV-AN, V29A, P62
[8]  
Low HP, 2001, IN VITRO CELL DEV-AN, V37, P141
[9]  
LOWRY OH, 1951, J BIOL CHEM, V193, P265
[10]   MEASUREMENT OF CYTOCHROME-P-450 DEPENDENT DEALKYLATION OF ALKOXYPHENOXAZONES IN HEPATIC S9S AND HEPATOCYTE HOMOGENATES - EFFECTS OF DICUMAROL [J].
LUBET, RA ;
NIMS, RW ;
MAYER, RT ;
CAMERON, JW ;
SCHECHTMAN, LM .
MUTATION RESEARCH, 1985, 142 (03) :127-131