Open AccessImpact of estrogen population pharmacokinetics on a QSP model of mammary stem cell differentiation into myoepithelial cells
Author(s) -
Justin Le Sauteur-Robitaille,
Zhe Yu,
Morgan Craig
Publication year - 2021
Publication title -
aims mathematics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.329
H-Index - 15
ISSN - 2473-6988
DOI - 10.3934/math.2021631
Subject(s) - myoepithelial cell , estrogen , population , estrogen receptor , stem cell , biology , cell , cancer research , pharmacokinetics , microbiology and biotechnology , cancer , endocrinology , pharmacology , breast cancer , medicine , immunology , genetics , immunohistochemistry , environmental health
Stem cell differentiation cascades are critical components of healthy tissue maintenance. Dysregulation in these systems can lead to serious diseases, including cancer. Myoepithelial mammary cells are produced from differentiated mammary stem cells in processes regulated, in part, by estrogen signalling and concentrations. To quantify and predict the production of mammary myoepithelial cell production by estrogen, we developed a mechanistic, quantitative systems pharmacology (QSP) model that includes the explicit characterization of free and unbound estrogen concentrations in circulation. Linking this model to a previously developed population pharmacokinetics model for ethinyl estradiol, a synthetic form of estrogen included in oral contraceptives, we predicted the effects of estrogen on myoepithelial cell development. Interestingly, pharmacokinetic intraindividual variability alone did not significantly impact on our modelos predictions, suggesting that combinations of physiological and pharmacokinetic variability drive heterogeneity in mechanistic QSP models. Our model is one component of an improved understanding of mammary myoepithelial cell production and development, and our results support the call for mechanistically constructed systems models for disease and pharmaceutical modelling.