| Project/Area Number |
05670464
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Gastroenterology
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| Research Institution | GIFU UNIVERSITY |
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Principal Investigator |
OHNISHI Hiroo GIFU UNIVERSITY SCHOOL OF MEDICINE,ASSISTANT PROFESSOR, 医学部附属病院, 講師 (40176954)
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| Co-Investigator(Kenkyū-buntansha) |
SUGIHARA Junichi GIFU UNIVERSITY SCHOOL OF MEDICINE,ASSISTANT PROFESSOR, 医学部附属病院, 講師 (70216323)
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| Project Period (FY) |
1993 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1995: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1994: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1993: ¥700,000 (Direct Cost: ¥700,000)
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| Keywords | Extracellular matrix / EHS gel / Primary cultured hepatocyte / Liver-specific functions / Albumin production / Ammonia detoxication / Hollow fiber cartridge / EHSgel / ブタ急性虚血性肝不全 / 動脈血ケント体比 / 肝癌由来株化細胞 / 肝細胞特異機能 / PVLA / 転写因子 / 転写制御因子 |
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| Research Abstract |
Culturing hepatocytes on different extracellular matrix (ECM) substrata including tissue culture plastic, type I collagen, Engelbreth-Holm-Swarm (EHS) gel and poly-N-p-vinylbenzyl-D-lactonamide (PVLA) regulated levels of mRNAs for cytoskeleton and liver specific genes. In hepatocytes on EHS gel, the ratio of albumin/beta-actin in mRNA levels was high and serially increased during cultute period, while the ratio was low and declined in cells on plastic substratum, type I collagen or PVLA.The changes in cellular levels of albumin mRNA which were regulated by ECM corresponded with those in the liver-specific transcription factor, hepatocyte nuclear factor-4 (HNF-4), which controls the the transcription of liver-specific genes.
A most important feature in the design of bioartificial liver is that bioreactor cells retain highly differentiated functions for prolonged periods. Hepatocyte functions were evaluated in perfused bioreactors, each containing of primary rat hepatocytes or transformed human liver cells (Hep G2) entrapped in EHS gel in hollow fiber modules. In vitro application of a gel entrapment bioartificial liver showed that albumin secretion and ureogenesis were observed to a greater extent in rat hepatocytes than in Hep G2 cells. The hybrid liver support system was developed consisting of plasma perfusion through porous hollow fiber modules inoculated with porcine hepatocytes in EHS gel. The system was examined in pigs with ischemic liver failure. During bioartificial liver support treatment, pigs with liver failures decreased serum ammonia levels. These findings suggested that primary hepatocyte was superior to the Hep G2 cell line as the source of hepatic function in a bio-artificial liver and that EHS gel hepatocyte culture system which combined with a hollow fiber module had useful advantages for bioartificial liver.
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