ELUCIDATING APOPTOTIC CELL DEATH IN CHO CELL BATCH FED-BATCH CULTURES

摘要

Chinese Hamster Ovary (CHO) cells are regarded as one of the industrial 'work-horses' for complex biotherapeutics production. In these processes, loss in culture viability occurs primarily via apoptosis, a genetically controlled form of cellular suicide. By applying microarray technology using our 'in-house' developed CHO cDNA array and a mouse oligonucleotide array for time profile expression analysis, the genetic circuitry that regulates and executes apoptosis induction can be carried out rapidly.We found that in both batch and fed-batch cultures, receptor-and mitochondrial-mediated apoptosis pathways play important roles in apoptosis induction. There are also several other minor pro-apoptotic genes that appear to be upregulated during apoptosisinduction in CHO cells. However, although these other genes had been implicated in apoptosis induction, their exact role in apoptosis induction has yet to be elucidated. By having a greater understanding of the regulatory circuitry of apoptosis relevantto cell culture processes, future effective strategies could be developed towards cell death prevention.