title: Numerical modelling of label-structured cell population growth using CFSE distribution data.
abstract: BACKGROUND
  The flow cytometry analysis of CFSE-labelled cells is currently one of the most informative experimental techniques for studying cell proliferation in immunology. The quantitative interpretation and understanding of such heterogenous cell population data requires the development of distributed parameter mathematical models and computational techniques for data assimilation.
  
  
  RESULTS
  The mathematical modelling of label-structured cell population dynamics leads to a hyperbolic partial differential equation in one space variable. The model contains fundamental parameters of cell turnover and label dilution that need to be estimated from the flow cytometry data on the kinetics of the CFSE label distribution. To this end a maximum likelihood approach is used. The Lax-Wendroff method is used to solve the corresponding initial-boundary value problem for the model equation. By fitting two original experimental data sets with the model we show its biological consistency and potential for quantitative characterization of the cell division and death rates, treated as continuous functions of the CFSE expression level.
  
  
  CONCLUSIONS
  Once the initial distribution of the proliferating cell population with respect to the CFSE intensity is given, the distributed parameter modelling allows one to work directly with the histograms of the CFSE fluorescence without the need to specify the marker ranges. The label-structured model and the elaborated computational approach establish a quantitative basis for more informative interpretation of the flow cytometry CFSE systems.
authors.affiliation: Institute of Numerical Mathematics, RAS, Moscow, Russia. valotis@pzlc.uni-wuerzburg.de
authors.forename: Tatyana
authors.initials: T
authors.lastname: Luzyanina
authors.forename: Dirk
authors.initials: D
authors.lastname: Roose
authors.forename: Tim
authors.initials: T
authors.lastname: Schenkel
authors.forename: Martina
authors.initials: M
authors.lastname: Sester
authors.forename: Stephan
authors.initials: S
authors.lastname: Ehl
authors.forename: Andreas
authors.initials: A
authors.lastname: Meyerhans
authors.forename: Gennady
authors.initials: G
authors.lastname: Bocharov
mesh_terms: D049109:Cell Proliferation; D005434:Flow Cytometry / Q000379:methods; D005452:Fluoresceins / Q000032:analysis*; D006801:Humans; D008214:Lymphocytes / Q000166:cytology / Q000502:physiology; D008954:Models, Biological; D013194:Staining and Labeling / Q000379:methods; D013388:Succinimides / Q000032:analysis*
chemical_list: C087165:5-(6)-carboxyfluorescein diacetate succinimidyl ester; D005452:Fluoresceins; D013388:Succinimides