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Metabolic Regulatory Network Kinetic Modeling with Multiple Isotopic Tracers for iPSCs
  • Wei Xie,
  • Keqi Wang,
  • Sarah Harcum
Wei Xie
Northeastern University

Corresponding Author:[email protected]

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Keqi Wang
Northeastern University
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Sarah Harcum
Clemson University
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The rapidly expanding market for regenerative medicines and cell therapies highlights the need to advance the understanding of cellular metabolisms and improve the prediction of cultivation production process for human induced pluripotent stem cells (iPSCs). In this paper, a metabolic kinetic model was developed to characterize underlying mechanisms of iPSC culture process, which can predict cell response to environmental perturbation and support process control. This model focuses on the central carbon metabolic network, including glycolysis, pentose phosphate pathway (PPP), tricarboxylic acid (TCA) cycle, and amino acid metabolism, which plays a crucial role to support iPSC proliferation. Heterogeneous measures of extracellular metabolites and multiple isotopic tracers collected under multiple conditions were used to learn metabolic regulatory mechanisms. Systematic cross-validation confirmed the model’s performance in terms of providing reliable predictions on cellular metabolism and culture process dynamics under various culture conditions. Thus, the developed mechanistic kinetic model can support process control strategies to strategically select optimal cell culture conditions at different times, ensure cell product functionality, and facilitate large-scale manufacturing of regenerative medicines and cell therapies.
07 Aug 2023Submitted to Biotechnology and Bioengineering
07 Aug 2023Submission Checks Completed
07 Aug 2023Assigned to Editor
07 Aug 2023Review(s) Completed, Editorial Evaluation Pending
14 Aug 2023Reviewer(s) Assigned
06 Sep 2023Editorial Decision: Revise Major
30 Oct 20231st Revision Received
30 Oct 2023Submission Checks Completed
30 Oct 2023Assigned to Editor
30 Oct 2023Review(s) Completed, Editorial Evaluation Pending
06 Nov 2023Reviewer(s) Assigned
15 Nov 2023Editorial Decision: Accept