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A Simple Method to Reduce both Lactic Acid and Ammonium Production in Industrial Animal Cell Culture

Fed-batch animal cell culture is the most common method for commercial production of recombinant proteins. However, higher cell densities in these platforms are still limited due to factors such as excessive ammonium production, lactic acid production, nutrient limitation, and/or hyperosmotic stress...

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Detalles Bibliográficos
Autores principales: Freund, Nathaniel W., Croughan, Matthew S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5855607/
https://www.ncbi.nlm.nih.gov/pubmed/29382079
http://dx.doi.org/10.3390/ijms19020385
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author Freund, Nathaniel W.
Croughan, Matthew S.
author_facet Freund, Nathaniel W.
Croughan, Matthew S.
author_sort Freund, Nathaniel W.
collection PubMed
description Fed-batch animal cell culture is the most common method for commercial production of recombinant proteins. However, higher cell densities in these platforms are still limited due to factors such as excessive ammonium production, lactic acid production, nutrient limitation, and/or hyperosmotic stress related to nutrient feeds and base additions to control pH. To partly overcome these factors, we investigated a simple method to reduce both ammonium and lactic acid production—termed Lactate Supplementation and Adaptation (LSA) technology—through the use of CHO cells adapted to a lactate-supplemented medium. Using this simple method, we achieved a reduction of nearly 100% in lactic acid production with a simultaneous 50% reduction in ammonium production in batch shaker flasks cultures. In subsequent fed-batch bioreactor cultures, lactic acid production and base addition were both reduced eight-fold. Viable cell densities of 35 million cells per mL and integral viable cell days of 273 million cell-days per mL were achieved, both among the highest currently reported for a fed-batch animal cell culture. Investigating the benefits of LSA technology in animal cell culture is worthy of further consideration and may lead to process conditions more favorable for advanced industrial applications.
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spelling pubmed-58556072018-03-20 A Simple Method to Reduce both Lactic Acid and Ammonium Production in Industrial Animal Cell Culture Freund, Nathaniel W. Croughan, Matthew S. Int J Mol Sci Article Fed-batch animal cell culture is the most common method for commercial production of recombinant proteins. However, higher cell densities in these platforms are still limited due to factors such as excessive ammonium production, lactic acid production, nutrient limitation, and/or hyperosmotic stress related to nutrient feeds and base additions to control pH. To partly overcome these factors, we investigated a simple method to reduce both ammonium and lactic acid production—termed Lactate Supplementation and Adaptation (LSA) technology—through the use of CHO cells adapted to a lactate-supplemented medium. Using this simple method, we achieved a reduction of nearly 100% in lactic acid production with a simultaneous 50% reduction in ammonium production in batch shaker flasks cultures. In subsequent fed-batch bioreactor cultures, lactic acid production and base addition were both reduced eight-fold. Viable cell densities of 35 million cells per mL and integral viable cell days of 273 million cell-days per mL were achieved, both among the highest currently reported for a fed-batch animal cell culture. Investigating the benefits of LSA technology in animal cell culture is worthy of further consideration and may lead to process conditions more favorable for advanced industrial applications. MDPI 2018-01-28 /pmc/articles/PMC5855607/ /pubmed/29382079 http://dx.doi.org/10.3390/ijms19020385 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Freund, Nathaniel W.
Croughan, Matthew S.
A Simple Method to Reduce both Lactic Acid and Ammonium Production in Industrial Animal Cell Culture
title A Simple Method to Reduce both Lactic Acid and Ammonium Production in Industrial Animal Cell Culture
title_full A Simple Method to Reduce both Lactic Acid and Ammonium Production in Industrial Animal Cell Culture
title_fullStr A Simple Method to Reduce both Lactic Acid and Ammonium Production in Industrial Animal Cell Culture
title_full_unstemmed A Simple Method to Reduce both Lactic Acid and Ammonium Production in Industrial Animal Cell Culture
title_short A Simple Method to Reduce both Lactic Acid and Ammonium Production in Industrial Animal Cell Culture
title_sort simple method to reduce both lactic acid and ammonium production in industrial animal cell culture
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5855607/
https://www.ncbi.nlm.nih.gov/pubmed/29382079
http://dx.doi.org/10.3390/ijms19020385
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