Adaptation for survival: Phenotype and transcriptome response of CHO cells to elevated stress induced by agitation and sparging

Pilot‐scale open‐channel raceways and flat‐panel photobioreactors maintain well‐mixed conditions under a wide range of mixing energy inputs

“…Detrimental impacts of turbulent mixing have also been demonstrated, with inhibition attributed to cell disruption from shear stress (Chalmers, 2015; Han & Yuan, 2004; Kunnen, Malas, Semeins, Bakker, & Peters, 2017; Richardson, Lannigan, & Macara, 2015; Sieck et al, 2014, 2013; Wang, Lü, Mao, & Long, 2014; Yi et al, 2010). For example, hybridoma cells suffer apoptosis at mixing energy inputs of 1.87 × 10 3 W·m −3 (Al‐Rubeai, Singh, Goldman, & Emery, 1995; Chalmers, 2015).…”

Euler–Lagrange approach to model heterogeneities in stirred tank bioreactors – Comparison to experimental flow characterization and particle tracking

“…So, cells are also experiencing fluctuating mechanical stress levels. Several works have been devoted to the study of the mechanical stress required to damage animal cells using either microfluidic flow contraction devices (Gregoriades et al, 2000;Godoy-Silva et al, 2009a,b;Nienow et al, 2013) or lab-scale stirred tank reactors (Sieck et al, 2013(Sieck et al, , 2014Nienow, 2006). These studies showed that free-suspended commercial cells such as CHO or insect cells are not sensitive to mechanical stress levels generated by agitation alone in bioreactors.…”

Scale-down of CHO cell fed-batch cultures

“…~290 W/kg) that were orders of magnitude higher than the estimated maximum [ε] generated from agitation in large-scale STRs. In contrast, when an agitation rate condition of 700 RPM (~0.5 W/kg) was applied in a 4 L bioreactor experiment done by Sieck et al 32 , reduced culture viable cell density and viability were observed compared to a standard agitation rate condition (267 RPM, ~0.03 W/kg). This stress level at which damage occurs is thus substantially lower than those reported by others.…”

“…More recently, with the advances of system biology tools and the publication of the CHO genome 26 , omics' studies (e.g. transcriptomics, proteomics, and metabolomics) have been increasingly applied in cell culture process development to identify genes related to recombinant protein productivity [27][28][29] , and to study different culture conditions that affect the culture performance 19,[30][31][32] . These studies have contributed to the fundamental understanding of CHO cell metabolism and resulted in improved process performances.…”

“…differences between scales) influence cell physiology and process performance. For example, Sieck et al 32,177 found that transcripts related to DNA damage and repair mechanisms were up-regulated when elevated shear forces from agitation and sparging were applied to a CHO cell culture.…”