School of Chemical Engineering, Institute for Molecular Biology and Genetics, Seoul National University, Seoul, 151-742, Korea.
Cytotechnology. 2000 Oct;34(1-2):151-8. doi: 10.1023/A:1008120313175.
To indentify a plausible large-scale production system forretroviral vector, three culture systems, i.e., batch culturewith medium exchange, microcarrier culture, and packed-bedreactor culture were compared. In batch cultures with mediumexchange, high cell concentrations were maintained for about amonth, and the harvested retroviral titer remained constant. Inmicrocarrier cultures, although cell growth was rapid, theretroviral titer was unexpectedly low, suggesting that the lowtiter was due either to serious damage to the retroviral vectoror to a reduction in the production rate of retroviral vector,caused by mechanical shear forces. Although the retroviral titer(maximum titer, 1.56 x 10(6)) in the packed-bedreactor was a little bit lower than that obtained in the batchculture with medium exchange (maximum titer, 1.91 x10(6)), continuous production made it possible to increasethe cumulative titer up to 16-fold of that from the batchculture with medium exchange. Moreover, as the packed-bedreactor system requires less labor and shows excellentvolumetric productivity in comparison to batch cultures withmedium exchanges, it will be an appropriate production systemfor retroviral vector in large quantities.
为了鉴定一种可行的逆转录病毒载体的大规模生产系统，我们比较了三种培养系统，即分批培养加培养基更换、微载体培养和填充床反应器培养。在分批培养加培养基更换中，细胞浓度可以维持在较高水平约一个月，收获的逆转录病毒滴度保持不变。在微载体培养中，虽然细胞生长很快，但逆转录病毒滴度却出人意料地低，这表明低滴度要么是由于逆转录病毒载体受到严重损伤，要么是由于机械剪切力导致逆转录病毒载体的生产速度降低。虽然填充床反应器中的逆转录病毒滴度（最高滴度为 1.56×10(6))略低于分批培养加培养基更换（最高滴度为 1.91×10(6))，但连续生产可以将累积滴度提高到分批培养加培养基更换的 16 倍。此外，与分批培养加培养基更换相比，填充床反应器系统需要的劳动力更少，体积产率更高，因此它将是一种适用于大量生产逆转录病毒载体的生产系统。
