1997 Fiscal Year Final Research Report Summary
Research system of toxicity for human liver cell lines
| Project/Area Number |
08557033
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Public health/Health science
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| Research Institution | Jikei University School of Medicine |
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Principal Investigator |
SHIMIZU Hidesuke Jikei University School of Medicine, Professor, 医学部, 教授 (80056879)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUURA Tomokazu Jikei University School of Medicine, Assistant, 医学部, 助手 (30199749)
SUZUKI Pul.Yuji Jikei University School of Medicine Assistant Professor, 医学部, 講師 (30163017)
HASUMURA Satoshi Jikei University School of Medicine, Assistant Professor, 医学部, 講師 (30189518)
NAGAMORI Seishi Jikei University School of Medicine, Associate Professor, 医学部, 助教授 (60119831)
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| Project Period (FY) |
1996 – 1997
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| Keywords | radial flow bioreactor / human liver cancer cell / mutagens / metabolism of toxicity |
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| Research Abstract |
Cell morphology and function for a newly developed hepatocytes culture system cmploying highly functional human liver cell line, FLC,cultured in a radial flow bioreactor were compared to cells grown in a conventional monolayr culture. The radial flow bioreactor consists of a vertically-extended cylindrical matrix comprised of porous glass bead microcarriers through which liquid medium flows from the periphery in toward the central axis generating a beneficial concentration gradient of exygen and nutrients while preventing excessive shear stresses or build up of waste products. The three dimensional culture system supports high-density and long-term viability. Scanning and transmission electron microscopy revealed that cells cultured in a monolayr system were flattened and extended with numerous cytoplasmic projections. Cells in the three-dimensional culture were spherical and covered with microvilli-like processes resembling liver cells in vivo. The cells were solidly attached on the surfaces and within the pores of the microcarriers in highly dense colonies. FLC cells metabolized antipyrine, nafamostat mesilate, and ammonia. This indicated that FLC cells were equiped with activities of cytochrome P450, carboxylesterase and urea cycle. Micronucleus research proved that FLC cells were available for investigation of mutagens. Results demonstrated that FLC cells in a radial flow bioreactor system provides a superior three-dimensional culture environment which allows cells to metabolize toxicities and this system had the ability to be an artificial liver to investigate human liver metabolism of toxicity.
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