Three-dimensional modeling of transport of nutrients for multicellular tumor spheroid culture in a microchannel
Three-dimensional modeling of transport of nutrients for multicellular tumor spheroid culture in a microchannel
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DOI：
10.1007/s10544-006-9035-1
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发表时间：
2007-06-01
影响因子：
2.8
通讯作者：
Li, Dongqing
中科院分区：
文献类型：
--
作者：
Hu, Guoqing;Li, Dongqing
研究了无血管肿瘤在微通道生物反应器中的生长动力学。建立了一个三维流动和营养物质输运模型，并结合多细胞肿瘤球体（MTS）生长模型，研究了营养物质（氧气和葡萄糖）的供应和分布对MTS生长的影响。基于EMT 6/Ro肿瘤细胞的数值模拟表明，连续流灌注比仅扩散的静态培养更有效地将营养物质输送到MTS。进一步证明，只要存在整体流动，单个肿瘤球体在早期的生长对流速和通道尺寸不敏感。然而，对于同一微通道中的多个肿瘤球体，增加灌注速度可以改善不利下游肿瘤球体的营养环境。在目前的微通道生物反应器中，施加在MTS上的流动剪切应力估计远低于影响MTS生长的临界值，这意味着仍有很大的空间来增加灌注速度以满足生长的肿瘤球体的更高的营养需求。
The growth dynamics of avascular tumors in a microchannel bioreactor is investigated. A three-dimensional flow and nutrient transport model, incorporating the multicellular tumor spheroid (MTS) growth model, has been developed to study the influence of nutrients (oxygen and glucose) supply and distribution on the MTS growth. Numerical simulations based on the EMT6/Ro tumor cells show that the continuous-flow perfusion is more efficient to deliver nutrients to the MTS than the diffusion-only static culture. It is further demonstrated that as long as there is bulk flow, the growth of a single tumor spheroid at the early stage is insensitive to the flow velocity and the channel size. For multiple tumor spheroids in the same microchannel, however, increasing the perfusion velocity can improve the nutrient environment for the disadvantageous downstream tumor spheroid. The flow shear stress exerting on the MTSs in the current microchannel bioreactor is estimated to be far below the critical value to affect the MTS growth, which means that there is still much room for increasing perfusion velocity to satisfy the higher nutrient requirement by the growing tumor spheroids.