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Using Metabolomics to Identify Cell Line-Independent Indicators of Growth Inhibition for Chinese Hamster Ovary Cell-Based Bioprocesses
Chinese hamster ovary (CHO) cells are widely used for the production of biopharmaceuticals. Efforts to improve productivity through medium design and feeding strategy optimization have focused on preventing the depletion of essential nutrients and managing the accumulation of lactate and ammonia. In...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281457/ https://www.ncbi.nlm.nih.gov/pubmed/32429145 http://dx.doi.org/10.3390/metabo10050199 |
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author | Alden, Nicholas Raju, Ravali McElearney, Kyle Lambropoulos, James Kshirsagar, Rashmi Gilbert, Alan Lee, Kyongbum |
author_facet | Alden, Nicholas Raju, Ravali McElearney, Kyle Lambropoulos, James Kshirsagar, Rashmi Gilbert, Alan Lee, Kyongbum |
author_sort | Alden, Nicholas |
collection | PubMed |
description | Chinese hamster ovary (CHO) cells are widely used for the production of biopharmaceuticals. Efforts to improve productivity through medium design and feeding strategy optimization have focused on preventing the depletion of essential nutrients and managing the accumulation of lactate and ammonia. In addition to ammonia and lactate, many other metabolites accumulate in CHO cell cultures, although their effects remain largely unknown. Elucidating these effects has the potential to further improve the productivity of CHO cell-based bioprocesses. This study used untargeted metabolomics to identify metabolites that accumulate in fed-batch cultures of monoclonal antibody (mAb) producing CHO cells. The metabolomics experiments profiled six cell lines that are derived from two different hosts, produce different mAbs, and exhibit different growth profiles. Comparing the cell lines’ metabolite profiles at different growth stages, we found a strong negative correlation between peak viable cell density (VCD) and a tryptophan metabolite, putatively identified as 5-hydroxyindoleacetaldehyde (5-HIAAld). Amino acid supplementation experiments showed strong growth inhibition of all cell lines by excess tryptophan, which correlated with the accumulation of 5-HIAAld in the culture medium. Prospectively, the approach presented in this study could be used to identify cell line- and host-independent metabolite markers for clone selection and bioprocess development. |
format | Online Article Text |
id | pubmed-7281457 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-72814572020-06-19 Using Metabolomics to Identify Cell Line-Independent Indicators of Growth Inhibition for Chinese Hamster Ovary Cell-Based Bioprocesses Alden, Nicholas Raju, Ravali McElearney, Kyle Lambropoulos, James Kshirsagar, Rashmi Gilbert, Alan Lee, Kyongbum Metabolites Article Chinese hamster ovary (CHO) cells are widely used for the production of biopharmaceuticals. Efforts to improve productivity through medium design and feeding strategy optimization have focused on preventing the depletion of essential nutrients and managing the accumulation of lactate and ammonia. In addition to ammonia and lactate, many other metabolites accumulate in CHO cell cultures, although their effects remain largely unknown. Elucidating these effects has the potential to further improve the productivity of CHO cell-based bioprocesses. This study used untargeted metabolomics to identify metabolites that accumulate in fed-batch cultures of monoclonal antibody (mAb) producing CHO cells. The metabolomics experiments profiled six cell lines that are derived from two different hosts, produce different mAbs, and exhibit different growth profiles. Comparing the cell lines’ metabolite profiles at different growth stages, we found a strong negative correlation between peak viable cell density (VCD) and a tryptophan metabolite, putatively identified as 5-hydroxyindoleacetaldehyde (5-HIAAld). Amino acid supplementation experiments showed strong growth inhibition of all cell lines by excess tryptophan, which correlated with the accumulation of 5-HIAAld in the culture medium. Prospectively, the approach presented in this study could be used to identify cell line- and host-independent metabolite markers for clone selection and bioprocess development. MDPI 2020-05-15 /pmc/articles/PMC7281457/ /pubmed/32429145 http://dx.doi.org/10.3390/metabo10050199 Text en © 2020 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 Alden, Nicholas Raju, Ravali McElearney, Kyle Lambropoulos, James Kshirsagar, Rashmi Gilbert, Alan Lee, Kyongbum Using Metabolomics to Identify Cell Line-Independent Indicators of Growth Inhibition for Chinese Hamster Ovary Cell-Based Bioprocesses |
title | Using Metabolomics to Identify Cell Line-Independent Indicators of Growth Inhibition for Chinese Hamster Ovary Cell-Based Bioprocesses |
title_full | Using Metabolomics to Identify Cell Line-Independent Indicators of Growth Inhibition for Chinese Hamster Ovary Cell-Based Bioprocesses |
title_fullStr | Using Metabolomics to Identify Cell Line-Independent Indicators of Growth Inhibition for Chinese Hamster Ovary Cell-Based Bioprocesses |
title_full_unstemmed | Using Metabolomics to Identify Cell Line-Independent Indicators of Growth Inhibition for Chinese Hamster Ovary Cell-Based Bioprocesses |
title_short | Using Metabolomics to Identify Cell Line-Independent Indicators of Growth Inhibition for Chinese Hamster Ovary Cell-Based Bioprocesses |
title_sort | using metabolomics to identify cell line-independent indicators of growth inhibition for chinese hamster ovary cell-based bioprocesses |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281457/ https://www.ncbi.nlm.nih.gov/pubmed/32429145 http://dx.doi.org/10.3390/metabo10050199 |
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