Cargando…
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...
Autores principales: | , |
---|---|
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 |
_version_ | 1783307136329056256 |
---|---|
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. |
format | Online Article Text |
id | pubmed-5855607 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT freundnathanielw asimplemethodtoreducebothlacticacidandammoniumproductioninindustrialanimalcellculture AT croughanmatthews asimplemethodtoreducebothlacticacidandammoniumproductioninindustrialanimalcellculture AT freundnathanielw simplemethodtoreducebothlacticacidandammoniumproductioninindustrialanimalcellculture AT croughanmatthews simplemethodtoreducebothlacticacidandammoniumproductioninindustrialanimalcellculture |