Human pluripotent stem cell (hPSC) populations are heterogeneous hindering their efficient expansion and differentiation to desired lineages. We developed a population balance equation model to describe and predict the dynamics of human embryonic stem cell (hESC) self-renewal. Intrinsic and extrinsic sources of population heterogeneity as well as experimental data were considered in the construction of the model. Solutions to the model were obtained primarily by Monte Carlo methods. Model parameters pertinent to cell growth, division and stem cell gene expression were calculated from experiments. Additional experiments were carried out to validate the simulation predictions. The contribution of intrinsic sources considered here to hESC heterogeneity was found to be almost 40%. Current efforts concentrate on expanding the model to include additional sources of heterogeneity stemming from hESC differentiation. The quantitative framework developed can complement and accelerate investigations on stem cell propagation or differentiation while reducing costly and labor-intensive experimental procedures.

Stem cell population heterogeneity: Development of a quantitative framework

243rd National Meeting (2012)

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