[Growth and metabolic characteristics and kinetic modeling of MDCK adherent cells cultured in basket bioreactors].

Authors

Minne Su, Yihao Sun, Qiao Yang, Manni Xie, Hao Yu, Yu Wang, Yue Wang, Zheng Gong, Bo Liu, Jiayou Zhang

Published in

Sheng wu gong cheng xue bao = Chinese journal of biotechnology. Volume 42. Issue 6. Pages 2794-2807. Jun 25, 2026.

Abstract

This study developed kinetic models to describe the growth and metabolism of MDCK adherent cells cultured in basket bioreactors. These models were used to predict cell density, nutrient consumption, and metabolite concentrations at key stages of the culture process in basket bioreactors, helping to overcome sampling limitations caused by environmental conditions and bioreactor design. Experimental data, including cell density and glucose and lactate levels were obtained at different time points from 5 L bioreactors. Model parameters were estimated by nonlinear fitting in MATLAB. Kinetic models were established based on the Logistic and Luedeking-Piret equations, and a perfusion dilution item was introduced considering the perfusion culture. The prediction performance of the models was evaluated based on the goodness-of-fit, regression, and error distribution. The models were then validated with independent experimental data from 40 L basket bioreactors. The results showed that MDCK cells cultured in the 5 L bioreactor entered the plateau phase between 96 h and 108 h, with the maximum cell density reaching (795.13±16.22)×10⁴ cells/mL. The specific growth rate peaked with a value of 1.01/d at the time point of 36 h. During the plateau phase, the maximum lactate production rate was 1.71 mmol/(L·h), while the glucose consumption rate reached 2.21 mmol/(L·h). The kinetic models derived from the 5 L bioreactor data showed good agreement with experimental results, with R² values exceeding 0.95. When being applied to validation data from three independent 40 L bioreactor batches, the models consistently achieved R² values above 0.95. Offline cell densities measured by digestion at 96 h and 120 h showed no significant differences from the model predictions (P=0.48, P=0.92). The results indicated that the kinetic models developed with 5 L bioreactor data could accurately predict the growth and metabolic behavior of MDCK cells in the 40 L system. In addition, the results demonstrated that the operational performance of the 40 L bioreactor was comparable to that of the 5 L system. This confirmed the reliability of the established models for scale-up applications. By quantifying key parameters, including the specific growth rate, glucose consumption rate, and lactate production rate, the models provide a sound theoretical basis for optimizing basket bioreactor processes. Moreover, they offer strong technical support for improving production efficiency and quality control in industrial-scale manufacturing.

PMID:
42343813
Bibliographic data and abstract were imported from PubMed on 25 Jun 2026.

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