Parameter estimation in a structured erythropoiesis model

Ackleh, Azmy S.; Thibodeaux, Jeremy J.

doi:10.3934/mbe.2008.5.601

Cited by 12 publications

(12 citation statements)

References 19 publications

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“…In fitting ODE‐based models to our population dynamics data, we were able to decouple the rates of various cell fate decisions for each subpopulation using parameter estimation similar to what has been performed in other cell‐based contexts (Ackleh and Thibodeaux, ; Task et al, ). The parameter sensitivity analyses were limited to the cell fate decision rates and did not include analysis of parameters such as plating efficiency during subculture or time spent in the different differentiation phases.…”

Section: Discussionmentioning

confidence: 99%

Improving efficiency of human pluripotent stem cell differentiation platforms using an integrated experimental and computational approach

Selekman

Das

Grundl

et al. 2013

Biotech & Bioengineering

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Human pluripotent stem cells (hPSCs) have an unparalleled potential for tissue engineering applications including regenerative therapies and in vitro cell-based models for studying normal and diseased tissue morphogenesis, or drug and toxicological screens. While numerous hPSC differentiation methods have been developed to generate various somatic cell types, the potential of hPSC-based technologies is hinged on the ability to translate these established lab-scale differentiation systems to large-scale processes to meet the industrial and clinical demands for these somatic cell types. Here, we demonstrate a strategy for investigating the efficiency and scalability of hPSC differentiation platforms. Using two previously reported epithelial differentiation systems as models, we fit an ODE-based kinetic model to data representing dynamics of various cell subpopulations present in our culture. This fit was performed by estimating rate constants of each cell subpopulation’s cell fate decisions (self-renewal, differentiation, death). Sensitivity analyses on predicted rate constants indicated which cell fate decisions had the greatest impact on overall epithelial cell yield in each differentiation process. In addition, we found that the final cell yield was limited by the self-renewal rate of either the progenitor state or the final differentiated state, depending on the differentiation protocol. Also, the relative impact of these cell fate decision rates was highly dependent on the maximum capacity of the cell culture system. Overall, we outline a novel approach for quantitative analysis of established laboratory-scale hPSC differentiation systems and this approach may ease development to produce large quantities of cells for tissue engineering applications.

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Section: Discussionmentioning

confidence: 99%

Improving efficiency of human pluripotent stem cell differentiation platforms using an integrated experimental and computational approach

Selekman

Das

Grundl

et al. 2013

Biotech & Bioengineering

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“…Those were complemented by Belair et al in 1995 [5] and Mahaffy et al in 1999 [6], where in both cases an age-structured partial differential equation (PDE) system was used to model human erythropoiesis following a phlebotomy. Later similar models by Ackley et al (2008) [7] and Fuertinger et al (2013) [8] were developed, where more physiological properties were displayed and a more detailed numerical evaluation of these models was done. In addition, discrete time models of RBC production have been developed and early references can be found in Edelstein-Keshet's book [9].…”

Section: History Of Erythropoiesis Modeling and Comparison With Our Amentioning

confidence: 99%

Mathematical Modeling of RBC Count Dynamics after Blood Loss

et al. 2018

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The regeneration of red blood cells (RBCs) after blood loss is an individual complex process. We present a novel simple compartment model which is able to capture the most important features and can be personalized using parameter estimation. We compare predictions of the proposed and personalized model to a more sophisticated state-of-the-art model for erythropoiesis, and to clinical data from healthy subjects. We discuss the choice of model parameters with respect to identifiability. We give an outlook on how extensions of this novel mathematical model could have an important impact for personalized clinical decision support in the case of polycythemia vera (PV). PV is a slow-growing type of blood cancer, where especially the production of RBCs is increased. The principal treatment targeting the symptoms of PV is bloodletting (phlebotomy), at regular intervals that are based on personal experiences of the physicians. Model-based decision support might help to identify optimal and individualized phlebotomy schedules.

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“…There is a growing amount of mathematical literature on the dynamics of erythropoiesis. This body of work includes model development, parameter estimation, numerical methods, and stability analysis (Ackleh 1999;Ackleh et al 2005Ackleh et al , 2006Ackleh and Thibodeaux 2008;Bélair and Mahaffy 2001;Mahaffy et al 1999).…”

Section: Introductionmentioning

confidence: 97%

Optimal Treatment Strategies for Malaria Infection

Thibodeaux

Schlittenhardt

2011

Bull Math Biol

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We develop a numerical method for estimating optimal parameters in a mathematical model of the within-host dynamics of malaria infection. The model consists of a quasilinear system of partial differential equations. Convergence theory for the computed parameters is provided. Following this analysis, we present several numerical simulations that suggest that periodic treatments that are in synchronization with the periodic bursting rate of infected erythrocytes are the most productive strategies.

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Parameter estimation in a structured erythropoiesis model

Cited by 12 publications

References 19 publications

Improving efficiency of human pluripotent stem cell differentiation platforms using an integrated experimental and computational approach

Improving efficiency of human pluripotent stem cell differentiation platforms using an integrated experimental and computational approach

Mathematical Modeling of RBC Count Dynamics after Blood Loss

Optimal Treatment Strategies for Malaria Infection

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