RT Journal Article
A1 C. Luni
A1 F.J. Doyle
A1 N. Elvassore

PB iet
T1 Cell population modelling describes intrinsic heterogeneity: a case study for hematopoietic stem cells
JN IET Systems Biology
VO 5
IS 3
SP 164
OP 173
AB The control of stem cell properties during in vitro expansion is of paramount importance for their clinical use. According to Food and Drug Administration (FDA) guidelines, phenotypic heterogeneity is a critical aspect influencing therapeutic response. Even if the authors ability to reduce heterogeneity were limited, the sources from which it arises should be well understood for safe clinical applications. The aim of this work was to describe theoretically the intrinsic cell population heterogeneity that is present even when cells are cultured in a perfectly homogeneous environment. A bivariate population balance model is developed to account for the heterogeneity in the number of receptors and receptor–ligand complexes per cell, and is coupled with a ligand conservation equation. As a case study, the model is applied to the hematopoietic stem cell expansion, considering the c-Kit receptor and stem cell factor pair. Results show the dependence of intrinsic heterogeneity from ligand concentration and the kinetics of its administration. By tracking the cell generations within the total population, the authors highlight intra- and an inter-generational contributions to total population heterogeneity. In terms of dimensionless variables, intrinsic heterogeneity is dependent on the ratio of the characteristic time of cell division to that needed by a newborn cell to reach its single-cell steady state. [Includes supplementary material]
K1 stem cell factor pair
K1 phenotypic heterogeneity
K1 cell culture
K1 safe clinical applications
K1 c-Kit receptor
K1 in vitro expansion
K1 therapeutic response
K1 intragenerational contributions
K1 bivariate population balance model
K1 cell population modelling
K1 intergenerational contributions
K1 ligand conservation equation
K1 single-cell steady state
K1 hematopoietic stem cells
K1 hematopoietic stem cell expansion
K1 intrinsic heterogeneity
K1 receptor-ligand complexes
K1 newborn cell
K1 intrinsic cell population heterogeneity
K1 dimensionless variables
K1 Food and Drug Administration guidelines
DO https://doi.org/10.1049/iet-syb.2009.0059
UL https://digital-library.theiet.org/;jsessionid=d2olnj6hpub0.x-iet-live-01content/journals/10.1049/iet-syb.2009.0059
LA English
SN 1751-8849
YR 2011
OL EN