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Valeric acid supplementation combined to mild hypothermia increases productivity in CHO cell cultivations

Paper ID Volume ID Publish Year Pages File Format Full-Text
2679 126 2016 9 PDF Available
Title
Valeric acid supplementation combined to mild hypothermia increases productivity in CHO cell cultivations
Abstract

•Valeric and butyric acid supplementation increased qp under mild hypothermia.•Supplementation with 1 mM valeric acid at 31 °C led to the highest productivity.•Valeric acid was less cytotoxic than butyric acid.•Percentage of cells in G0 + G1 phase was higher at 31 °C, mainly with valeric acid.•The proliferation state of cells [S/(G0 + G1) ratio] inversely correlated with qp.

Aiming at increasing productivity in mammalian cell processes, mild hypothermia and supplementation with short-chain fatty acids have been investigated in literature, but usually separately. The combined effects of butyric acid and hypothermia were investigated in a few studies, but despite the lower cytotoxicity of valeric acid no reports were found on its use under low temperatures. In this work, DOE was used to compare supplementation with both butyrate and valerate at 31, 34 and 37 °C to enhance recombinant protein productivity in a CHO cell process. Due to the promising results obtained with valerate, this fatty acid was further investigated. According to the results obtained, 1 mM valeric acid at 31 °C enables high cell viabilities, higher product titres and increases cell specific productivity (qp) by approximately 4-fold. Cell cycle analysis showed that at 31 °C, especially with valerate, a higher percentage of cells was in G0 + G1 phase. Overall, an inverse relation between qp and cell proliferation state [S/(G0 + G1) ratio] was observed. To our knowledge, this is the first work describing the effects of valeric acid under mild hypothermia on CHO cell cultivations. The results provide a promising tool to increase qp under lower proliferation rates, which can be very useful to develop robust high-cell-density, high-productivity perfusion processes.

Keywords
CHO cell culture; Cultivation temperature; Butyrate and valerate supplementation; Valeric acid and mild hypothermia; Cell viability and product titre; Cell specific productivity (qp)
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Valeric acid supplementation combined to mild hypothermia increases productivity in CHO cell cultivations
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biochemical Engineering Journal - Volume 114, 15 October 2016, Pages 101–109
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us