Hepatocyte bioreactor system for long term culture of...

Chemistry: molecular biology and microbiology – Virus or bacteriophage – except for viral vector or...

Reexamination Certificate

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C435S239000, C435S383000, C435S370000, C435S375000, C424S093700

Reexamination Certificate

active

07575911

ABSTRACT:
A rotating wall vessel is used as a culture vessel and bioreactor for the cultivation of hepatocytes in the form of spheroids to generate a culture with many properties of the intact liver. These properties include enzyme activity comparable to fresh cells and long-term maintenance of viability and cellular function for periods on the order of months. The cultures may be used to produce hepatocyte products, evaluate-metabolism of an agent, propagate Hepatitis C virus and test agents as inhibitors of this virus. Thus, the culture system disclosed herein makes long term functional cultivation of human hepatocytes feasible.

REFERENCES:
patent: 5624839 (1997-04-01), Yada et al.
Li, et al., “A Simplified Method for the Culturing of Primary Adult Rat and Human Hepatocytes as Multicellular Spheroids,” In Vitro Cell. Dev. Biol., 28A:673-677, Sep.-Oct. 1992.
Battle, et al., “Progressive Maturation Resistance to Microcystin-LR Cytotoxicity in Two Different Hepatospheroidal Models,” Cell Biology and Toxicology, 1999, pp. 3-12.
Clejan, et al., “Effects of Simulated Microgravity on DU 145 Human Prostate Carcinoma Cells,” Biotechnology and Bioengineering, vol. 50; 1996, pp. 587-597.
Dabos, et al., “The Simulated Microgravity Environment Maintains Key Metabolic Functions and Promotes Aggregation of Primary Procine Hepatocytes,” Biochimica et Biophysica Acta 1526 (2001) pp. 119-130.
Notification of Transmittal of the International Search Report or the Declaration; International Search Report, Jun. 30, 2003, pp. 1-7.

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