Purpose: To develop multi-compartment mechanistic models of dynamics of stem and functional cell populations in epithelium after irradiation.

Methods and materials: We present two models, with three (3C) and four (4C) compartments respectively. We use delay differential equations, and include accelerated proliferation, loss of division asymmetry, progressive death of abortive stem cells, and turnover of functional cells. The models are used to fit experimental data on the variations of the number of cells in mice mucosa after irradiation with 13 Gy and 20 Gy. Akaike information criteria (AIC) was used to evaluate the performance of each model.

Results: Both 3C and 4C models provide good fits to experimental data for 13 Gy. Fits for 20 Gy are slightly poorer and may be affected by larger uncertainties and fluctuations of experimental data. Best fits are obtained by imposing constraints on the fitting parameters, so to have values that are within experimental ranges. There is some degeneration in the fits, as different sets of parameters provide similarly good fits.

Conclusions: The models provide good fits to experimental data. Mechanistic approaches like this can facilitate the development of mucositis response models to non-standard schedules/treatment combinations not covered by datasets to which phenomenological models have been fitted. Studying the dynamics of cell populations in multifraction treatments, and finding links with induced toxicity, is the next step of this work.

目的：建立照射后上皮中干细胞和功能细胞群体动力学的多室机制模型。

方法和材料：我们提供两个模型，分别具有三个（3C）和四个（4C）隔室。我们使用延迟微分方程，包括加速增殖，分裂不对称性丧失，流产干细胞进行性死亡和功能性细胞更新。该模型用于拟合13 Gy和20 Gy照射后小鼠粘膜细胞数目变化的实验数据。赤池信息标准（AIC）用于评估每个模型的性能。

结果：3C和4C模型都非常适合13 Gy的实验数据。20 Gy的拟合度稍差，可能会受到较大不确定性和实验数据波动的影响。通过在拟合参数上施加约束来获得最佳拟合，以使其值在实验范围内。由于不同的参数集提供了类似的良好拟合，所以拟合中会出现一些退化。

结论：这些模型与实验数据非常吻合。这样的机械方法可以促进粘膜炎反应模型针对非标准方案/治疗组合的开发，这些非标准方案/治疗组合未包含适用于现象学模型的数据集。研究多组分治疗中细胞群的动力学，并寻找与诱导毒性的联系，是这项工作的下一步。