Rapid Identification of Chinese Hamster Ovary Cell Apoptosis and Its Potential Role in Process Robustness Assessment

Currently, the assessment of process robustness is often time-consuming, labor-intensive, and material-intensive using process characterization studies. Therefore, a simple and time-saving method is highly needed for the biopharmaceutical industry. Apoptosis is responsible for 80% of Chinese hamster...

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Main Authors: Shang Xiao, Qiang Li, Jinlong Jiang, Chengxiao Huo, Hao Chen, Meijin Guo
Format: Article
Language:English
Published: MDPI AG 2023-03-01
Series:Bioengineering
Subjects:
Online Access:https://www.mdpi.com/2306-5354/10/3/357
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author Shang Xiao
Qiang Li
Jinlong Jiang
Chengxiao Huo
Hao Chen
Meijin Guo
author_facet Shang Xiao
Qiang Li
Jinlong Jiang
Chengxiao Huo
Hao Chen
Meijin Guo
author_sort Shang Xiao
collection DOAJ
description Currently, the assessment of process robustness is often time-consuming, labor-intensive, and material-intensive using process characterization studies. Therefore, a simple and time-saving method is highly needed for the biopharmaceutical industry. Apoptosis is responsible for 80% of Chinese hamster ovary (CHO) cell deaths and affects the robustness of the cell culture process. This study’s results showed that a more robust process can support cells to tolerate apoptosis for a longer time, suggesting that the robustness of the process could be judged by the ability of cells to resist apoptosis. Therefore, it is necessary to establish a rapid method to detect the apoptosis of CHO cells. In trying to establish a new method for detecting apoptosis in large-scale cell cultures, glucose withdrawal was studied, and the results showed that CHO cells began to apoptose after glucose was consumed. Then, the concentration of extracellular potassium increased, and a prolongation of apoptosis time was observed. Further study results showed that the process with poor robustness was associated with a higher proportion of apoptosis and extracellular potassium concentration, so potassium could be used as a biochemical index of apoptosis. The strategy we present may be used to expedite the assessment of process robustness to obtain a robust cell culture process for other biologics.
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spelling doaj.art-bb4ce1eb669a4f63a2506762b38666892023-11-17T09:40:09ZengMDPI AGBioengineering2306-53542023-03-0110335710.3390/bioengineering10030357Rapid Identification of Chinese Hamster Ovary Cell Apoptosis and Its Potential Role in Process Robustness AssessmentShang Xiao0Qiang Li1Jinlong Jiang2Chengxiao Huo3Hao Chen4Meijin Guo5State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, ChinaState Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, ChinaState Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, ChinaShanghai Biological Products Research Institute Co., Ltd., Shanghai 200051, ChinaShanghai Biological Products Research Institute Co., Ltd., Shanghai 200051, ChinaState Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, ChinaCurrently, the assessment of process robustness is often time-consuming, labor-intensive, and material-intensive using process characterization studies. Therefore, a simple and time-saving method is highly needed for the biopharmaceutical industry. Apoptosis is responsible for 80% of Chinese hamster ovary (CHO) cell deaths and affects the robustness of the cell culture process. This study’s results showed that a more robust process can support cells to tolerate apoptosis for a longer time, suggesting that the robustness of the process could be judged by the ability of cells to resist apoptosis. Therefore, it is necessary to establish a rapid method to detect the apoptosis of CHO cells. In trying to establish a new method for detecting apoptosis in large-scale cell cultures, glucose withdrawal was studied, and the results showed that CHO cells began to apoptose after glucose was consumed. Then, the concentration of extracellular potassium increased, and a prolongation of apoptosis time was observed. Further study results showed that the process with poor robustness was associated with a higher proportion of apoptosis and extracellular potassium concentration, so potassium could be used as a biochemical index of apoptosis. The strategy we present may be used to expedite the assessment of process robustness to obtain a robust cell culture process for other biologics.https://www.mdpi.com/2306-5354/10/3/357CHOapoptosisglucose withdrawalrobustnessprocess characterization
spellingShingle Shang Xiao
Qiang Li
Jinlong Jiang
Chengxiao Huo
Hao Chen
Meijin Guo
Rapid Identification of Chinese Hamster Ovary Cell Apoptosis and Its Potential Role in Process Robustness Assessment
Bioengineering
CHO
apoptosis
glucose withdrawal
robustness
process characterization
title Rapid Identification of Chinese Hamster Ovary Cell Apoptosis and Its Potential Role in Process Robustness Assessment
title_full Rapid Identification of Chinese Hamster Ovary Cell Apoptosis and Its Potential Role in Process Robustness Assessment
title_fullStr Rapid Identification of Chinese Hamster Ovary Cell Apoptosis and Its Potential Role in Process Robustness Assessment
title_full_unstemmed Rapid Identification of Chinese Hamster Ovary Cell Apoptosis and Its Potential Role in Process Robustness Assessment
title_short Rapid Identification of Chinese Hamster Ovary Cell Apoptosis and Its Potential Role in Process Robustness Assessment
title_sort rapid identification of chinese hamster ovary cell apoptosis and its potential role in process robustness assessment
topic CHO
apoptosis
glucose withdrawal
robustness
process characterization
url https://www.mdpi.com/2306-5354/10/3/357
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AT jinlongjiang rapididentificationofchinesehamsterovarycellapoptosisanditspotentialroleinprocessrobustnessassessment
AT chengxiaohuo rapididentificationofchinesehamsterovarycellapoptosisanditspotentialroleinprocessrobustnessassessment
AT haochen rapididentificationofchinesehamsterovarycellapoptosisanditspotentialroleinprocessrobustnessassessment
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