神经干细胞球在生物反应器内培养的模拟计算

Simulation of the Growth of Neurosphere Cultured in Bioreactors

采用元胞自动机技术建立的模拟神经球生长的动态模型,结合反应器中培养的神经球内部养分的扩散传递模型,求解了神经干细胞球内出现坏死细胞核的临界神经球尺寸和坏死细胞核的扩大规律,以及反应器内养分浓度的变化情况。计算结果表明,坏死细胞核的出现与体外培养条件有一定关系:神经球培养密度、培养基养分浓度和培养基与神经球之间的传质情况等都有一定程度的影响;但是坏死细胞核的出现主要取决于神经球的尺寸,过大的神经球内必定会出现坏死细胞核,即使在生物反应器中良好的外部培养条件下也不可能抑制它的出现。此外,神经球内由于氧缺乏而形成的坏死细胞核的出现要早于由于葡萄糖缺乏时的情况,并且坏死细胞核一旦出现,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。本文所建立的元胞自动机(C e llu larau tom ata,CA)模型及各种生物反应器培养条件下神经球内的传质模型可以很好的模拟神经球的生长过程。

When the size of a neurosphere cultured in vitro reaches a certain critical value, a necrotic core will appear inside the neurosphere because of the limitation of oxygen or other nutrients transport from medium to the cells in the neurasphere. Large necrotic core will greatly reduce the expansion of NSCs. The cellular automaton （CA） model is applied 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 model with the nutrient diffusion analysis in bioreactors. The calculation results indicate that the culture conditions, such as seeding density, the concentration of nutrients in medium and the mass transfer coefficient between a neurosphere and medium, have some effects on the appearance of the necrotic core. However, the necrotic core mainly depends on the inner diffusion. It will certainly appear if the size of the neurosphere is large enough even the outside mass transfer is in a good condition in bioreactors. Additionally, the appearance of the necrotic core resulting from the shortage of oxygen is earlier than that caused by the limitation of glucose. And the growth of the necrotic core is very fast after its appearance, and the whole neurosphere may become necrotic. The model developed with cellular automaton and mass transfer is a good qualitative representation of NSCs growth in bioreactors.