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\begin{document}

\title{Metabolic Regulatory Network Kinetic Modeling with Multiple Isotopic
Tracers for iPSCs}



\author[1]{Wei Xie}%
\author[1]{Keqi Wang}%
\author[2]{Sarah Harcum}%
\affil[1]{Northeastern University}%
\affil[2]{Clemson University}%


\vspace{-1em}



  
  \date{May 23, 2024}


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\begin{abstract}
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.%
\end{abstract}%



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