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An unstructured model of metabolic and temperature dependent cell cycle arrest in hybridoma batch and fed-batch cultures

Paper ID Volume ID Publish Year Pages File Format Full-Text
3078 149 2015 14 PDF Available
Title
An unstructured model of metabolic and temperature dependent cell cycle arrest in hybridoma batch and fed-batch cultures
Abstract

•Proposes an experimental approach to formulate and refine temperature dependent cell cycle models.•Identifies the cell cycle effects including G0 in a hybridoma cell line induced by different temperature shifts time points.•Predicts cell growth, unstructured metabolism, and productivity at different temperature profiles.

Cell productivity in fed-batch processes can be increased by cell cycle arrest through mild hypothermia. However, hypothermia can simultaneously reduce cell growth, which is regulated by the cell cycle. Consequently, the time point for the temperature shift is important and requires optimization while considering the cell cycle. An unstructured cell cycle model which includes the distribution of proliferating (G1, S, G2/M) and arrested cells (G0) has been proposed in order to predict the time point of temperature shift in fed-batch cultures. A model development and analysis framework that enables the evaluation of the required model parameters is described. The parameters are estimated from (fed)-batch cultivations, carried out at 37 °C and at 33 °C in order to characterize temperature dependency. The batch cultures are also used to evaluate substrate depletion and fed-batch cultures are used to study the impact of metabolite accumulation on the cell cycle. The reliability of the proposed framework for parameter estimation is validated using a mAb-producing hybridoma cell culture and the model predicts hypothermic transitions within the cell population at different shift time points. In conclusion, this framework can be used to optimize the time point of the temperature shift, which is commonly adjusted in industrial fed-batch processes in order to obtain a good balance between temperature induced growth limitation and cell cycle specific enhanced productivity.

Keywords
Cell cycle model; Hypothermia; Temperature control; Cell arrest; Cell cycle specific productivity
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An unstructured model of metabolic and temperature dependent cell cycle arrest in hybridoma batch and fed-batch cultures
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biochemical Engineering Journal - Volume 93, 15 January 2015, Pages 260–273
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
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us