1996 Fiscal Year Final Research Report Summary
Development of Hybrid Artificial Liver with Isolated Hepatocytes in Extracorporeal Circulation
| Project/Area Number |
06454381
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Digestive surgery
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| Research Institution | Shiga University of Medical Science |
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Principal Investigator |
KODAMA Masashi Shiga university of Medical Science First Department of Surgery, Professor and Chairman, 医学部, 教授 (50079836)
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| Project Period (FY) |
1994 – 1995
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| Keywords | Artificial Liver Support / Hepatocytes / Hybrid Artificial Liver / Liver Failure / Collagen Gel |
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| Research Abstract |
In an attempt to develop a hybrid artificial liver (HAL) using isolated hepatocytes, we prepared hollow fiber modules with hepatocytes entrapped in collagen gel and evaluated the HAL devices in hepatic failure models. And we studied the hypothermic preservation (4ﾟC) of hepatocytes entrapped in collagen gel, for the purpose of storage of the HAL devices.
In rats experiments, the modules contained 4*10^7 rat hepatocytes were evaluated by extracorporeal hemoperfusion. In ischemic hepatic failure models, the device revealed ammonia removal and gluconeogenesis. Drug (galactosamin) induced acute hepatic failure rats showed the improvement of total bile acid and GOT in extracorporeal hemoperfusion. The devices demonstrated the supporting failing functions on host livers.
In rabbits experiments, the modules contained 3.5*10^8 rabbit hepatocytes were evaluated. Perfusion culture was performed and demonstrated good maintenance of differentiated liver functions of albumin secretion, ureogenesis and ammonia removal at Day 0. Perfusion solution showed appearance of a protein with same molecular weight as in rabbit serum. The devices were evaluated as a HAL by extracorporeal hemoperfusion using one or two modules in anhepatic rabbits. In the single HAL groups, blood pressure were significantly maintained. Increase in serum ammonia was inhibited and survival time were significantly prolonged. In the double HAL groups, lactic acid, prothrombin time and Fisher ratio were improved significantly.
These studies provided the evidence that our HAL system included detoxicating, synthetic and metabolic functions, and it may be clinically useful in the future.
We studied the preservation of hepatocytes entrapped in collagen gel in 4ﾟC University of Wisconsin solution. Preserved hepatocytes in our system showed round-shaped morphology in phase-difference and scanning electron microscopy. They maintained adequate functional capability even after 14 days of preservation.
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Research Products
(16 results)
