Document Detail


Physiological responses of CHO cells to repetitive hydrodynamic stress.
MedLine Citation:
PMID:  19405151     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A majority of the previous investigations on the hydrodynamic sensitivity of mammalian cells have focused on lethal effects as determined by cell death or lysis. In this study, we investigated the effect of hydrodynamic stress on CHO cells in a fed-batch process using a previously reported system which subjects cells to repetitive, high levels of hydrodynamic stress, quantified by energy dissipation rate (EDR). The results indicated that cell growth and monoclonal antibody production of the test cells were very resistant to the hydrodynamic stress. Compared to the control, no significant variation was observed at the highest EDR tested, 6.4 x 10(6) W/m(3). Most product quality attributes were not affected by intense hydrodynamic stress either. The only significant impact was on glycosylation. A shift of glycosylation pattern was observed at EDR levels at or higher than 6.0 x 10(4) W/m(3), which is two orders of magnitude lower than the EDR where physical cell damage, as measured by lactate dehydrogenase release, was observed. While not as extensively investigated, a second monoclonal antibody produced in a different CHO clone exhibited the same glycosylation change at an intensive EDR, 2.9 x 10(5) W/m(3). Conversely, a low EDR of 0.9 x 10(2) W/m(3) had no effect on the glycosylation pattern. As 6.0 x 10(4) W/m(3), the lowest EDR that triggers the glycosylation shift, is about one order of magnitude higher than the estimated, maximum EDR in typically operated, large-scale stirred tank bioreactors, further studies in a lower EDR range of 1 x 10(3)-6.0 x 10(4) W/m(3) are needed to assess the glycosylation shift effect under typical large-scale bioreactor operation conditions. Follow-up studies in stirred tanks are also needed to confirm the glycosylation shift effect and to validate the repetitive hydrodynamic stress model.
Authors:
Ruben Godoy-Silva; Jeffrey J Chalmers; Susan A Casnocha; Laura A Bass; Ningning Ma
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Biotechnology and bioengineering     Volume:  103     ISSN:  1097-0290     ISO Abbreviation:  Biotechnol. Bioeng.     Publication Date:  2009 Aug 
Date Detail:
Created Date:  2009-06-29     Completed Date:  2009-08-11     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7502021     Medline TA:  Biotechnol Bioeng     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1103-17     Citation Subset:  IM    
Copyright Information:
Copyright 2009 Wiley Periodicals, Inc.
Affiliation:
Bioprocess R&D, Global Biologics, Pfizer, Inc., 700 Chesterfield Parkway West, Chesterfield, Missouri 63017, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Antibodies, Monoclonal / biosynthesis
CHO Cells
Cricetinae
Cricetulus
Eukaryotic Cells / physiology*
Glycosylation
Recombinant Proteins / biosynthesis
Stress, Mechanical*
Stress, Physiological*
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Recombinant Proteins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Mice lacking adenylyl cyclase-5 cope badly with repeated restraint stress.
Next Document:  A two-phase partitioning airlift bioreactor for the treatment of BTEX contaminated gases.