神经干细胞球生长动力学模型

神经干细胞的体外大规模培养对于细胞移植治疗中枢神经系统受损及各种神经退行性疾病有重大意义。体外呈球状生长的神经干细胞球在长大到一定尺寸之后，有可能在其内部由于养分缺乏而形成坏死细胞，这对于干细胞的有效扩增是极为不利的。因此，模拟神经球的动态生长过程并分析出现坏死细胞的临界神经球尺度对于神经干细胞的大规模扩增有重要意义。本研究采用元胞自动机技术建立了模拟神经球生长的动态模型，并结合神经球内养分的扩散传递模型，求解神经干细胞球内出现坏死细胞的临界神经球尺寸以及坏死细胞的扩大规律。计算结果表明，坏死细胞的出现与体外培养条件有一定关系；坏死细胞的出现主要取决于神经球的尺寸，其外部再好的培养条件也不可能抑制坏死的出现。此外，计算结果还表明，神经球内由于氧缺乏而形成的坏死细胞的出现要早于由于葡萄糖缺乏时的情况，并且坏死细胞一旦出现，其增长速度就非常快，有可能很快使整个神经球成为坏死细胞球。本研究所建立的CA模型及神经球内的传质模型可以很好的模拟神经球的生长过程。

A Cellular Automaton Model for the Growth Dynamics of Neural Stem Cell Spheroid

Purpose Cell transplantation for the diseased central nervous system requires a substantial amount of neural stem cells(NSCs)to be generated in vitro.High expansion rates of NSCs in culture are thus crucial for the clinical application.When the size of a neurosphere cultured in vitro reaches a certain critical value,a necrotic core appears inside the neurosphere because of the lack of oxygen or other nutrients transport from medium to the cells in the neurosphere.Large necrotic core will greatly reduce the expansion of NSCs.Therefore,it is important to simulate the dynamic process of the growth of neurospheres and analyze the critical size of the neurosphere at which the necrotic core appears.Methods A cellular automaton approach was proposed in this article to model the growth of NSCs in sphere state.The appearance and enlargement of the necrotic core in a neurosphere is calculated by coupling the CA(cellular automaton) model with the nutrient diffusion analysis.Results The calculation results indicated that the culture conditions,including seeding density,concentration of nutrients in medium and the mass transfer coefficient between a neurosphere and medium,have influence on the appearance of the necrotic core.The necrotic core mainly depends on the inner diffusion.Necrotic core appeared when the size of neurosphere was large enough even the outside mass transfer was in a good condition.Additionally,the appearance of necrotic core resulted from the shortage of oxygen was earlier than that caused by the limitation of glucose.And the growth of necrotic core was very fast after its appearance,and the whole neurosphere may become necrotic.Conclusion The established automaton model could simulate NSCs growth in vitro.