Cell population modeling can contribute to the optimization and standardization of the efficient maintenance and differentiation of stem cells. In this work, a population balance equation (PBE) model was constructed for the heterogeneous self-renewal of hESCs with a physiological state vector comprising elements pertinent to hESC proliferation and pluripotency. Model parameters pertinent to cell growth, division and marker expression were calculated from experimental data. Additional experiments for the self-renewal of hESCs were carried out to validate the model. The PBE model successfully depicts both the proliferation of hESCs and maintenance of their pluripotency in a heterogeneous population. Contribution of cell division on Nanog expression heterogeneity was quantified for the first time at about 20% predicted by the PBE model. The model has further been extended to represent multiple cell types under differentiation conditions. By doing this, stem cell self-renewal and differentiation activities could be captured at population level.

Modeling and experimental analysis of human pluripotent stem cell self-renewal and differentiation in a heterogeneous population

245th National Meeting (2013)

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