PUBLICATION Mammalian Cell Designers’ Laboratory

MISSION

Our mission is to engineer next-generation mammalian cell factories
for the production of complex biotherapeutics.
By integrating synthetic biology, genome engineering, and autonomous experimentation,
we aim to transform cell line development from empirical optimization into a predictive engineering discipline.

Journal Articles

Autophagy and apoptosis of recombinant Chinese hamster ovary cells during fed‐batch culture: Effect of nutrient supplementation
Author
Young Kue Han*, Tae Kwang Ha, So Jeong Lee, Jae Seong Lee, Gyun Min Lee‡
Journal
Biotechnology and Bioengineering
Vol
108(9)
Page
2182-2192
Year
2017~

Upon nutrient depletion during recombinant Chinese hamster ovary (rCHO) cell batch culture, cells are subjected to apoptosis, type I programmed cell death (PCD), and autophagy which can be type II PCD or a cell survival mechanism. To investigate the effect of nutrient supplementation on the two PCDs and protein production in rCHO cells, an antibody-producing rCHO cell line was cultivated in batch and fed-batch modes. The feed medium containing glucose, amino acids, and vitamins was determined through flask culture tests and used in bioreactor cultures. In the bioreactor cultures, the nutrient feedings extended the culture longevity and enhanced antibody production. In addition, cells in the fed-batch culture showed delayed onset of both apoptosis and autophagy, compared with those in the batch culture. The inhibition of apoptosis was demonstrated by a decreased amount of cleaved caspase-7 protein and less fragmentation of chromosomal DNA. Concurrently, reduced LC3 conversion, from LC3-I to LC3-II, was observed in cells that received the feeds. Cultivation with pharmacological autophagy inducer (rapamycin) or inhibitor (bafilomycin A1) indicated that autophagy is necessary for the cells to survive under nutrient depletion. Taken together, the delayed and relieved cell death by nutrient supplementation could improve antibody production.