A model of hematopoietic stem cell proliferation under the influence of a chemotherapeutic agent in combination with a hematopoietic inducing agent

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Background: Hematopoiesis is a complex process that encompasses both pro-mitotic and anti-mitotic stimuli. Pharmacological agents used in chemotherapy have a prominent anti-mitotic effect. The approach of inhibiting cell proliferation is rational with respect to the rapidly dividing malignant cells. However, it poses a serious problem with respect to cell proliferation of cell types required for the 'house-keeping' operations of the human body. One such affected system is hematopoiesis. Chemotherapy induced anemia is an undesired side effect of chemotherapy that can lead to serious complications. Patients exhibiting anemia or leukopenia during chemotherapy are frequently administered a hematopoietic inducing agent that enhances hematopoiesis. Methods. In previous work, we derived a mathematical model consisting of a set of delay differential equations that was dependent on the effect of a hematopoietic inducing agent. The aim of the current work was to formulate a mathematical model that captures both the effect of a chemotherapeutic agent in combination with a hematopoietic inducing agent. Steady state solutions and stability analysis of the system of equations is performed and numerical simulations of the stem cell population are provided. Results: Numerical simulations confirm that our mathematical model captures the desired result which is that the use of hematopoietic agents in conjunction with chemotherapeutic agents can decrease the negative secondary effects often experienced by patients. Conclusions: The proposed model indicates that the introduction of hematopoietic inducing agents have clinical potential to offset the deleterious effects of chemotherapy treatment. Furthermore, the proposed model is relevant in that it enhances the understanding of stem cell dynamics and provides insight on the stem cell kinetics. © 2014 Mouser et al.; licensee BioMed Central Ltd.

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Theoretical Biology and Medical Modelling



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