Scale-up of animal cell culture systems

1998 ◽  
pp. 135-154 ◽  
Author(s):  
Bryan Griffiths ◽  
Wolfgang Noe
2020 ◽  
Vol 212 ◽  
pp. 115329 ◽  
Author(s):  
Chao Li ◽  
Xiaonuo Teng ◽  
Huadong Peng ◽  
Xiaoping Yi ◽  
Yingping Zhuang ◽  
...  

2020 ◽  
Author(s):  
David Humbird

“Cultured meat” technologies aim to replace conventional meat with analogous or alternative bioproducts from animal cell culture. Developers of these technologies claim their products, also known as “cell-based” or “cultivated” meat, will be safer and more environmentally friendly than conventional meat while offering improved farm-animal welfare. To these ends, Open Philanthropy commissioned this assessment of cultured meat’s potential to measurably displace the consumption of conventional meat.Recognizing that the scalability of any cultured-meat products must in turn depend on the scale and process intensity of animal cell production, this study draws on techno-economic analysis and due-diligence perspectives in industrial fermentation and upstream biopharmaceuticals to assess the extent to which animal cell culture could be scaled like a fermentation process.The analysis identifies a number of significant barriers to the scale-up of animal cell culture. Bioreactor design principles indicate a variety of issues associated with bulk cell growth in culture: Low growth rate, metabolic inefficiency, catabolite and CO2 inhibition, and bubble-induced cell damage will all limit practical bioreactor volume and attainable cell density. With existing bioreactor designs and animal cell lines, a significant engineering effort would be required to address even one of these issues.Economic challenges are further examined. Equipment and facilities with adequate microbial contamination safeguards are expected to have high capital costs. Suitable formulations of amino acids and protein growth factors are not currently produced at scales consistent with food production, and their projected costs at scale are likewise high. The replacement of amino-acid media with plant protein hydrolysates is discussed and requires further study.Capital- and operating-cost analyses of conceptual cell-mass production facilities indicate production economics that would likely preclude the affordability of their products as food. The analysis concludes that metabolic efficiency enhancements and the development of low-cost media from plant hydrolysates are both necessary but insufficient conditions for the measurable displacement of conventional meat by cultured meat.


2020 ◽  
Vol 14 ◽  
Author(s):  
Shogo Ozawa ◽  
Toshitaka Miura ◽  
Jun Terashima ◽  
Wataru Habano ◽  
Seiichi Ishida

Background: In order to avoid drug-induced liver injury (DILI), in vitro assays, which enable the assessment of both metabolic activation and immune reaction processes that ultimately result in DILI, are needed. Objective: In this study, the recent progress in the application of in vitro assays using cell culture systems is reviewed for potential DILI-causing drugs/xenobiotics and a mechanistic study on DILI, as well as for the limitations of in vitro cell culture systems for DILI research. Methods: Information related to DILI was collected through a literature search of the PubMed database. Results: The initial biological event for the onset of DILI is the formation of cellular protein adducts after drugs have been metabolically activated by drug metabolizing enzymes. The damaged peptides derived from protein adducts lead to the activation of CD4+ helper T lymphocytes and recognition by CD8+ cytotoxic T lymphocytes, which destroy hepatocytes through immunological reactions. Because DILI is a major cause of drug attrition and drug withdrawal, numerous in vitro systems consisting of hepatocytes and immune/inflammatory cells, or spheroids of human primary hepatocytes containing non-parenchymal cells have been developed. These cellular-based systems have identified DILIinducing drugs with approximately 50% sensitivity and 90% specificity. Conclusion: Different co-culture systems consisting of human hepatocyte-derived cells and other immune/inflammatory cells have enabled the identification of DILI-causing drugs and of the actual mechanisms of action.


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