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

机译:化疗药物与造血诱导剂联合作用下的造血干细胞增殖模型

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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.
机译:背景造血是一个复杂的过程,包括促有丝分裂和抗有丝分裂刺激。化学疗法中使用的药物具有显着的抗有丝分裂作用。对于迅速分裂的恶性细胞,抑制细胞增殖的方法是合理的。但是,这对于人体“内务”操作所需的细胞类型的细胞增殖构成了严重的问题。一种这样的受影响的系统是造血系统。化学疗法引起的贫血是化学疗法的不良副作用,可能导致严重的并发症。在化疗过程中表现出贫血或白细胞减少症的患者经常接受增强造血功能的造血诱导剂。方法在先前的工作中,我们推导了一个数学模型,该模型由一组延迟微分方程组成,该方程取决于造血诱导剂的作用。当前工作的目的是建立一个数学模型,该模型同时捕获化学治疗剂和造血诱导剂的作用。对方程组进行稳态解和稳定性分析,并对干细胞群体进行数值模拟。结果数值模拟证实我们的数学模型捕获了理想的结果,即造血剂与化疗剂的结合使用可以减少患者经常经历的负面副作用。结论所提出的模型表明,引入造血诱导剂具有抵消化学疗法的有害作用的临床潜力。此外,所提出的模型具有相关性,因为它增强了对干细胞动力学的理解并提供了对干细胞动力学的洞察力。

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