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Adaptation of Chinese hamster ovary cells to low culture temperature: Cell growth and recombinant protein production

Paper ID Volume ID Publish Year Pages File Format Full-Text
25702 43591 2006 10 PDF Available
Title
Adaptation of Chinese hamster ovary cells to low culture temperature: Cell growth and recombinant protein production
Abstract

Recombinant Chinese hamster ovary (rCHO) cells producing erythropoietin (EPO) and rCHO cells producing follicle-stimulating hormone (FSH) showed a significant increase in specific productivity (q) when grown at 32 °C compared to 37 °C. However, low culture temperature suppressed cell growth, and therefore, did not increase volumetric productivity as much as q. In an attempt to increase the volumetric productivity through improvement of hypothermic growth, EPO producing rCHO (CHO-EPO) cells and FSH producing rCHO (CHO-FSH) cells were adapted at 32 °C in a repeated batch mode using spinner flasks. Cell growth of both CHO-EPO and CHO-FSH gradually improved during adaptation at 32 °C. Specific growth rates of CHO-EPO and CHO-FSH cells at 32 °C, through adaptation, were increased by 73% and 20%, respectively. During adaptation at 32 °C, mRNA levels of cold-inducible RNA-binding protein (CIRP) of both rCHO cell lines did not change significantly, suggesting that CIRP expression may not be the only cause for growth suppression at low culture temperature. Unlike cell growth, the recombinant protein production of both rCHO cell lines was not increased during adaptation due to decreased specific productivities. The specific EPO productivity and specific FSH productivity were decreased by 49% and 22%, respectively. Southern blot analyses showed that the decreased specific productivities were not due to the loss of foreign gene copies. Taken together, improvement of hypothermic cell growth by adaptation does not appear to be applicable for enhanced recombinant protein production, since specific productivity decreases during adaptation to the low culture temperature.

Keywords
Adaptation; CHO cells; Cold-inducible RNA-binding protein (CIRP); Erythropoietin (EPO); Follicle-stimulating hormone (FSH); Hypothermia
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Publisher
Database: Elsevier - ScienceDirect
Journal: Journal of Biotechnology - Volume 122, Issue 4, 20 April 2006, Pages 463–472
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
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Full-text PDF Download
Online Support
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