Mathematical Models of Dividing Cell Populations: Application to CFSE Data

Abstract

Abstract. Flow cytometric analysis using intracellular dyes such as CFSE is a powerful experimental tool which can be used in conjunction with mathematical modeling to quantify the dynamic behavior of a population of lymphocytes. In this survey we begin by providing an overview of the mathematically relevant aspects of the data collection procedure. We then present an overview of the large body of mathematical models, along with their assumptions and uses, which have been proposed to describe the dynamics of proliferating cell populations. While much of this body of work has been aimed at modeling the generation structure (cells per generation) of the proliferating population, several recent models have considered the more fundamental task of modeling CFSE histogram data directly. Such models are analyzed and recent results are discussed. Finally, directions for future research are suggested.

Analysis of variability in estimates of cell proliferation parameters for cyton-based models using CFSE-based flow cytometry data

“…There is considerable experimental evidence [8,13,14] that supports the cyton model, and it has an advantage over models such as (3.4) in that it directly connects cell population numbers to probability distributions describing times at which cells in a given generation will divide or die. Identifying these distributions for populations of lymphocytes exposed to speci c environmental stimuli allows for a detailed quantitative description of the adaptive immune response.…”

Mathematical modeling reveals differential effects of erythropoietin on proliferation and lineage commitment of human hematopoietic progenitors in early erythroid culture

“…In particular, the Smith-Martin model that takes into account progression of cells through the cell cycle, has been successfully used to predict and model population dynamics of in vitro erythropoiesis. [21][22][23][24][25] We have combined immunophenotyping, proliferation analysis and cytokine dependence to refine the analysis of early erythroid culture of CD34 + cells isolated from human peripheral blood (PB). Isolated PB CD34 + cells are CMP, and the appearance of detectable surface levels of the erythroid marker CD36 is the earliest identifier of progenitors restricted to the megakaryocyte/erythroid lineage.…”

Preface. Distributed Parameter Systems in Immunology

“…Proliferating cell populations are the central subject of studies in immunology. An overview of mathematical models of differing complexity (random birthdeath-, fixed cycle-, Smith-Martin-, probabilistic-and label-structured PDE models) developed so far for describing the cell growth kinetics and the estimation of the turnover parameters is reviewed in the paper by Banks and Thompson [4]. It covers a broad range of issues related to data collection (based on using intracellular dyes such as CFSE and flow cytometry), model formulation, parameter estimation and ranking of different mathematical models.…”