Document Detail


Engineering considerations for process development in mammalian cell cultivation.
MedLine Citation:
PMID:  19929819     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Mammalian cell cultivation plays a great role in producing protein therapeutics in the last decades. Many engineering parameters are considered for optimization during process development in mammalian cell cultivation, only shear and mixing are especially highlighted in this paper. It is believed that shear stress due to agitation has been over-estimated to damage cells, but shear may result in nonlethal physiological responses. There is no cell damage in the regions where bubbles form, break up and coalescence, but shear stress becomes significant in the wake of rising bubbles and causes great damage to cells in bubble burst regions. Mixing is not sufficient to provide homogeneous dissolved oxygen tension, pH, CO2 and nutrients in large-scale bioreactors, which can bring severe problems for cell growth, product formation and process control. Scale-down reactors have been developed to address mixing and shear problems for parallel operations. Engineering characterization in conventional and recently developed scale-down bioreactors has been briefly introduced. Process challenges for cultivation of industrial cell lines in high cell densities as well as cultivation of stem cells and other human cells for regenerative medicine, tissue engineering and gene therapy are prospected. Important techniques, such as micromanipulation and nanomanipulation (optical tweezers) for single cell analysis, computational fluid dynamics (CFD) for shear and mixing characterization, and miniaturized bioreactors, are being developed to address those challenges.
Authors:
Hu Zhang; Weixiang Wang; Chunshan Quan; Shengdi Fan
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Current pharmaceutical biotechnology     Volume:  11     ISSN:  1873-4316     ISO Abbreviation:  Curr Pharm Biotechnol     Publication Date:  2010 Jan 
Date Detail:
Created Date:  2010-03-18     Completed Date:  2010-06-17     Revised Date:  2010-08-31    
Medline Journal Info:
Nlm Unique ID:  100960530     Medline TA:  Curr Pharm Biotechnol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  103-12     Citation Subset:  IM    
Affiliation:
Department of Chemical Engineering, University of Adelaide, South Australia, 5005, Australia. hu.zhang@adelaide.edu.au
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MeSH Terms
Descriptor/Qualifier:
Bioreactors*
Cell Culture Techniques / methods*
Cell Proliferation
Cells, Cultured / physiology*
Mechanotransduction, Cellular / physiology*
Tissue Engineering / methods*

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


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